Cesium carbonate → 6-[(2-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid

HRID 985333Notes

Reaction equation

HRID 985333 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([C:10]([O-:12])=[O:11])=[C:8]([CH3:13])[S:7][C:6]=2[CH:14]=1.Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]2[CH:22]=[C:23]([C:25]([N:27]3[CH2:31][CH2:30][C@@H:29]([OH:32])[CH2:28]3)=[O:26])[S:24][C:17]=12.C([O-])([O-])=O.[Cs+].[Cs+].O[Li].O>>[OH:32][C@@H:29]1[CH2:30][CH2:31][N:27]([C:25]([C:23]2[S:24][C:17]3[C:18](=[N:19][CH:20]=[CH:21][C:16]=3[O:1][C:2]3[CH:3]=[CH:4][C:5]4[C:9]([C:10]([OH:12])=[O:11])=[C:8]([CH3:13])[S:7][C:6]=4[CH:14]=3)[CH:22]=2)=[O:26])[CH2:28]1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 168937Lithium hydroxide, monohydrateHCID 207677587-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridineHCID 178435028HCID 178435028, compound

Product 1

HCID 207677606-[(2-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acidYield 45%

Procedure

This material was prepared from the reaction of methyl 6-hydroxy-2-methylbenzo[b]thiophene-3-carboxylate 11a (283 mg, 1.00 mmole) with 7-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine 4a and Cs2CO3 (977 mg, 3.00 mmole) in a manner as previously described for example 1. The crude product was then reacted with LiOH.H2O (227 mg, 5.4 mmole) in a manner similar to that described for example 11c to give a yellow solid (202 mg, 45%). 1H NMR (DMSO-d6, 300 MHz) δ8.58 (1H, d, J=5.31 Hz), 8.44 (1H, d, J=8.84 Hz), 8.14, 8.07 (1H, s), 8.00 (1H, s), 7.39 (1H, dd, J=2.40, 8.97 Hz), 6.78 (1H, d, J=5.56 Hz), 4.38, 4.33 (1H, br s), 4.01-3.91 (1H, m), 3.68-3.56 (2H, m), 3.49-3.22 (2H, m), 2.81 (3H, s), 2.07-1.79 (2H, m).

Sources & evidence

ORD record
ord-6b8d336d1ee24868ad2cc402e89df8b6
Source dataset
uspto-grants-2005_03
Patent number
US06869962B2

Reaction notes

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