Indazole and azaindazole Btk inhibitors

1. A compound of Formula (I)

wherein:

X 1 is N or C(H);

X 2 is N or C(R 6 );

R 1 is H, C 1-3 akyl, or —CH 2 —R 1a , wherein R 1a is phenyl or pyridyl;

R 6 is H or C 1-3 alkyl;

R 7 is:

(a.) a group of the formula —C(O)N(R 7a )(R 7b ), wherein R 7a and R 7b are independently H or C 1-3 alkyl; or alternatively, R 7a and R 7b together with the N to which they are attached form a 5- to 6-membered heterocyclyl optionally containing 1 additional heteroatom selected from N or O;

(b.) Cy, wherein Cy is phenyl or a 5- or 6-membered heteroaryl containing 1 to 3 N ring atoms; wherein Cy is unsubstituted or substituted by 1 to 2 R c substituents selected from:

(i.) C 1-4 alkyl,

(ii.) a group of the formula —C(R 7d ) 2 CO 2 H,

wherein R 7d is H or C 1-3 alkyl;

(iii.) —CH 2 CH 2 OCH 3 ; or

(iv.) tetrahydropyranyl;

or alternatively, two R c substituents, together with the atoms to which they are attached form a 5- to 6-membered heterocyclyl containing 1 N ring atom;

(c.) —C(O)OH;

(d.) H;

(e.) C 1-3 alkyl; or

(f.) C 1-3 fluoroalkyl;

R 8 is H, C 1-3 alkyl or C 1-3 hydroxyalkyl;

R 9 is:

 or

a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein X 2 is C(R 6 ).

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein X 1 and X 2 are both C(H).

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is H.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 7 is

(a.) a group of the formula —C(O)N(R 7a )(R 7b ), wherein R 7a and R 7b are independently H or methyl; or alternatively, R 7a and R 7b together with the N to which they are attached form a morpholinyl ring;

(b.) Cy,wherein Cy is phenyl, pyrazolyl, or pyridinyl; wherein Cy is unsubstituted or substituted by 1 to 2 R c substituents selected from:

(i.) C 1-4 alkyl,

(ii.) a group of the formula —C(R 7d ) 2 CO 2 H,

wherein R 7d is H or methyl;

(iii.) —CH 2 CH 2 OCH 3 ; or

(iv.) tetrahydropyranyl;

(c.) —C(O)OH;

(d.) H;

(e.) methyl; or

(f.) trifluoromethyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 8 is hydroxymethyl or methyl.

7. A compound which is:

3-amino-5-[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-1H-indazole-7-carboxylic acid,

2-[3-(3-amino-6-methyl-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

3-amino-5-[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-1H-indazole-7-carboxamide,

2-{3-[3-amino-7-(trifluoromethyl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl}-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

3-amino-5-[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-1-methyl-1H-indazole-7-carboxamide,

2-[3-{3-amino-7-[1-(1-methylethyl)-1H-pyrazol-4-yl]-1H-indazol-5-yl}-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

3-amino-5-(3-{[(4-tert-butyl-2-fluorophenyl)carbonyl]amino}-2-methylphenyl)-1H-indazole-7-carboxamide,

3-amino-5-[3-({[2-fluoro-4-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]carbonyl}amino)-2-methylphenyl]-1H-indazole-7-carboxamide,

2-{3-[3-amino-7-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl}-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

2[3-(3-3-(3-amino-7-pyridin-3-yl-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

3-amino-5[3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-N-methyl-1H-indazole-7-carboxamide,

2-{3[3-amino-1-(pyridin-4-ylmethyl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl}-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

N-{3[3-amino-7-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-2-methylphenyl}-4-tert-butylbenzamide,

2-{3-[3-amino-7-(morpholin-4-ylcarbonyl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl}-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

N-{3-[3-amino-7-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-2-methylphenyl1}-4-tert-butyl-2-fluorobenzamide,

3-amino-5-[3-(6-tert-butyl-8-fluoro-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)-2-(hydroxymethyl)phenyl]-1H-indazole-7-carboxamide,

2-[3-{3-amino-7-[-1-(1-methylethyl)-1H-pyrazol-3-yl]-1H-indazol-5-yl}-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

N-{3-[3-amino-7-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-2-(hydroxymethyl)phenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide,

2-[3-(3-amino-7-phenyl-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

2-[3-(3-amino-1H-pyrazolo[4,3-b]pyridin-5-yl)-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

2-[3-(3-amino-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(hydroxymethyl)phenyl]-6-tert-butyl-8-fluorophthalazin-1(2H)-one,

2-(3-(3-amino-7-(pyridin-2-yl)-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl)-6-(tert-butyl)-8-fluorophthalazin-1(2H)-one,

2-(4-(3-amino-5-(3-(6-(tert-butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-indazol-7-yl)-1H-pyrazol-1-yl)acetic acid,

2-(4-(3-amino-5-(3-(6-(tert-butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-indazol-7-yl)-1H-pyrazol-1-yl)-2-methylpropanoic acid,

2-(3-(3-amino-7-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl)-6-(tert-butyl)-8-fluorophthalazin-1(2H)-one,

2-(3-(3-amino-7-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl)-6-(tert-butyl)-8-fluorophthalazin-1(2H)-one,

2-(3-(3-amino-7-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl)-6-(tert-butyl)-8-fluorophthalazin-1(2H)-one,

2-(3-(3-amino-7-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-1H-indazol-5-yl)-2-(hydroxymethyl)phenyl)-6-(tert-butyl)-8-fluorophthalazin-1(2H)-one,

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.