2-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde → 2-Chloro-4-morpholin-4-yl-6-[4(thiazole-2-sulfonyl)-piperidin-1-ylmethyl]-thieno[3,2-d]pyrimidine

HRID 391136Notes

Reaction equation

HRID 391136 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][N:4]=[C:3]1[S:7]([CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)(=[O:9])=[O:8].[Cl:16][C:17]1[N:18]=[C:19]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:20]2[S:25][C:24]([CH:26]=O)=[CH:23][C:21]=2[N:22]=1>>[Cl:16][C:17]1[N:18]=[C:19]([N:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)[C:20]2[S:25][C:24]([CH2:26][N:13]3[CH2:14][CH2:15][CH:10]([S:7]([C:3]4[S:2][CH:6]=[CH:5][N:4]=4)(=[O:9])=[O:8])[CH2:11][CH2:12]3)=[CH:23][C:21]=2[N:22]=1

Participants

3

Reactant 2

HCID 457899852-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehydeHCID 669340182-(Piperidin-4-ylsulfonyl)thiazole hydrochloride

Product 1

HCID 866235432-Chloro-4-morpholin-4-yl-6-[4(thiazole-2-sulfonyl)-piperidin-1-ylmethyl]-thieno[3,2-d]pyrimidineYield 31.9%

Procedure

4-(Thiazole-2-sulfonyl)-piperidine HCl salt (124 mg) was reacted with 2-chloro-4-morpholin-4-yl-thieno[3,2-d]ppimidine-6-carbaldehyde 10 (130 mg) using standard reductive amination conditions. Aqueous work-up, purification on silica and trituration with hot ethyl acetate yielded 2-chloro-4-morpholin-4-yl-6-[4(thiazole-2-sulfonyl)-piperidin-1-ylmethyl]-thieno[3,2-d]pyrimidine (73 mg), which was reacted with 2-aminopyrimidine-5-boronic acid in General Procedure A. Purification on silica yielded 415. NMR (CDCl3): 2.03-2.18 (4H, m), 2.18-2.22 (2H, m), 3.12-3.16 (2H, m), 3.39-3.46 (1H, m), 3.84 (2H, s), 3.90-3.93 (4H, m), 4.03-4.06 (4H, m), 5.20 (2H, br), 7.26 (1H, s), 7.79 (1H, d, J=3.0), 8.11 (1H, d, J=3.0), 9.29 (2H, s) MS (ESI+): MH+ 559.13 (100%)

Workup

  1. customAqueous work-up, purification on silica and trituration with hot ethyl acetate

Sources & evidence

ORD record
ord-42334b5f780445caa976d0929a125769
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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