Methanesulfonyl chloride → [4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone

HRID 30160Notes

Reaction equation

C=O.[NH2:3][C:4]1[N:5]=[C:6]([NH:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[S:7][C:8]=1[C:9]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([F:19])[C:12]=1[F:20])=[O:10].[CH3:28][S:29](Cl)(=[O:31])=[O:30].C(N(C(C)C)CC)(C)C>>[NH2:3][C:4]1[N:5]=[C:6]([NH:21][CH:22]2[CH2:27][CH2:26][N:25]([S:29]([CH3:28])(=[O:31])=[O:30])[CH2:24][CH2:23]2)[S:7][C:8]=1[C:9]([C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([F:19])[C:12]=1[F:20])=[O:10]

Participants

Reactant 3

HCID 31297Methanesulfonyl chloride

HCID 81531Diisopropylethylamine

HCID 86602686HCID 86602686, compound

Product 1

HCID 11655245[4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanoneYield 90%

Procedure

[4-Amino-2-(piperidin-4-ylamino)thiazol-5-yl]-(2,3-difluoro-6-methoxy-phenyl)methanone methanone (0.05 g, 0.14 mmol) (Example 8) was treated with methanesulfonyl chloride in a manner similar to Example 9 except that diisopropylethyl amine was additionally used as a catalyst to give 50 mg (90% yield) of [4-amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone. 1H NMR (DMSO−d6, 300 MHz) δ1.57 (m, 2H, CH2), 1.92 (m, 2H, CH2), 2.85 (m, 5H, SCH3 & NCH2), 3.53 (m, 2H, NCH2), 3.6-4.0 (broad,1H, CH), 3.88(s, 3H, OCH3), 6.72 (m,1H, Aromatic), 7.42 (m,1H, Aromatic), 7.6 (2× brd, 1H, NH), 7.8 (brd, 1H, NH), 7.99 (m, 1H, Aromatic), 9.0 (brd, 1H, NH). LR/LC/MS: (M+H): compatible with 446. Ki CDK1=0.001 μM; Ki CDK2=0.001 μM; Ki CDK4=0.002 μM.

Sources & evidence

ORD record: ord-d3d7d3bc843448179251223ff144660f
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423053B2

Reaction notes

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