3,4-Dihydro-2H-pyran-6-boronic acid pinacol ester → 5-amino-2-(2,6-difluorophenyl)-N-[5-(3,4-dihydro-2H-pyran-6-yl)-1-methyl-pyrazol-4-yl]thiazole-4-carboxamide

HRID 521946Notes

Reaction equation

HRID 521946 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[NH:8][C:9]([C:11]1[N:12]=[C:13]([C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[S:14][C:15]=1[NH:16]C(=O)OC(C)(C)C)=[O:10].[O:32]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][CH2:35][CH2:34][CH2:33]1>>[NH2:16][C:15]1[S:14][C:13]([C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])=[N:12][C:11]=1[C:9]([NH:8][C:3]1[CH:4]=[N:5][N:6]([CH3:7])[C:2]=1[C:33]1[O:32][CH2:37][CH2:36][CH2:35][CH:34]=1)=[O:10]

Participants

3

Reactant 2

HCID 164141963,4-Dihydro-2H-pyran-6-boronic acid pinacol esterHCID 86713771tert-butyl 4-(5-chloro-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-(2,6-difluorophenyl)thiazol-5-ylcarbamate

Product 1

HCID 734384625-amino-2-(2,6-difluorophenyl)-N-[5-(3,4-dihydro-2H-pyran-6-yl)-1-methyl-pyrazol-4-yl]thiazole-4-carboxamideYield 8%

Procedure

Following the procedure for Example 101 starting from tert-butyl (4-((5-chloro-1-methyl-1H-pyrazol-4-yl)carbamoyl)-2-(2,6-difluorophenyl)thiazol-5-yl)carbamate and 3,4-dihydro-2H-pyran-6-boronic acid pinacol ester gave 102 as a white solid (25 mg, 8% over two steps). 1H NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.18 (s, 1H), 7.34-7.28 (m, 1H), 7.06-6.98 (m, 2H), 6.13 (s, 2H), 5.11 (t, J=3.9 Hz, 1H), 4.25 (t, J=5.1 Hz, 2H), 3.89 (s, 3H), 2.32-2.26 (m, 2H), 2.03-1.96 (m, 2H). LCMS (ES+) m/z 418 (M+1).

Sources & evidence

ORD record
ord-d9b818358c334a5d96ef4ef60a7621a6
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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