METHODS OF MAKING A MODULATOR OF HEMOGLOBIN

1 . (canceled)

2 . A process for preparing a compound of formula I:

comprising:

(i) contacting a compound of formula 1a:

with a metalating reagent and carbon dioxide to form a compound of formula 2a:

(ii) contacting a compound of formula 2a with tert-butyl(chloro)diphenylsilane and imidazole to form a compound of formula 3a:

(iii) contacting a compound of formula 3a with a compound of formula 4

to form a compound of formula 5a:

(iv) contacting a compound of formula 5a with a compound of formula 6:

to form a compound of formula 7a:

(v) deprotecting a compound of formula 7a to form a compound of formula I.

3 . (canceled)

4 . (canceled)

5 . The process of claim 2 , wherein the metalating agent is isopropyl magnesium chloride.

6 . The process of claim 2 , wherein step (iii) comprise a coupling agent and base.

7 . The process of claim 6 , wherein the coupling agent is N,N,N′,N′-Tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate, and the base is diisopropylethylamine.

8 . The process of claim 2 , wherein step (iv) comprise triphenylphosphine and diisopropyl azodicarboxylate.

9 . The process of claim 2 , wherein step (v) comprise tetrabutylammonium fluoride (TBAF).

10 . (canceled)

11 . (canceled)

12 . (canceled)

13 . A process for preparing a compound of formula I:

comprising:

(i) contacting a compound of formula 2 or a compound of formula 9:

wherein R 1 is H or a hydroxy protecting group;

with a compound of formula 10:

to form a compound of formula 11:

(ii) reducing and deprotecting a compound of formula 11 to provide a compound of formula I.

14 . The process of claim 13 , further comprising:

(ii) contacting a compound of formula 12:

with a compound of formula 13:

wherein:

R 2 is H or leaving group; and

R 3 is H or an amine protecting group;

to form a compound of formula 14:

and

(iii) deprotecting a compound of formula 14 to form a compound of formula 10.

15 . The process of claim 14 , wherein R 3 is H, —C(O)—O—C(CH 3 ) 3 , or —C(O)—O—CH 2 -phenyl.

16 . The process of claim 13 , further comprising:

contacting a compound of formula 12:

with a compound of formula 13:

wherein:

R 2 is H or leaving group; and R 3 is H; or

R 2 and R 3 , together with the atoms to which they are attached, join together to form a heterocyclic ring;

to form a compound of formula 10.

17 . The process of claim 14 , wherein R 2 is H or tosyl.

18 . A process for preparing a compound of formula I:

comprising:

(i) converting a compound of formula 5:

wherein PG is a hydroxy protecting group;

to form a compound of formula 15:

wherein LG is a leaving group;

(ii) contacting a compound of formula 15 with a compound of formula 12:

to form a compound of formula 11a:

(iii) reducing and deprotecting a compound of formula 11a to provide a compound of formula I.

19 .- 34 . (canceled)

35 . A compound of the formula:

or a salt thereof.

36 . The compound of claim 35 , wherein the compound is of the formula:

or a salt thereof.

37 . The compound of claim 35 , wherein the compound is of the formula:

or a salt thereof.