3,4-Dihydro-2H-pyran-6-boronic acid pinacol ester → 5-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)thiazole-4-carboxamide

HRID 1185361Notes

Reaction equation

C(OC([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[N:20]([CH3:21])[N:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[N:26]=[C:27](Br)[S:28][C:29]=2[NH:30]C(=O)OC(C)(C)C)=[O:24])[CH2:12][CH2:11]1)=O)CCC.[O:39]1[C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][CH2:42][CH2:41][CH2:40]1>>[NH2:30][C:29]1[S:28][C:27]([CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][O:39]2)=[N:26][C:25]=1[C:23]([NH:22][C:17]1[CH:18]=[N:19][N:20]([CH3:21])[C:16]=1[N:13]1[CH2:12][CH2:11][CH:10]([CH2:9][NH2:8])[CH2:15][CH2:14]1)=[O:24]

Participants

Reactant 2

HCID 164141963,4-Dihydro-2H-pyran-6-boronic acid pinacol ester

HCID 58464898tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate

Product 1

HCID 584647735-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(tetrahydro-2H-pyran-2-yl)thiazole-4-carboxamideYield 20%

Procedure

Following the procedure for Example 281, tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate and 3,4-dihydro-2H-pyran-6-boronic acid pinacol ester gave 290 as a yellow solid (27 mg, 20% over three steps). 1H NMR (400 MHz, d4-MeOD) δ 7.34 (s, 1H), 4.46-4.41 (m, 1H), 4.02-3.95 (m, 1H), 3.63 (s, 3H), 3.67-3.51 (m, 1H), 3.12-2.97 (m, 4H), 2.53 (d, J=6.6 Hz, 2H), 2.07-1.98 (m, 1H), 1.97-1.79 (m, 1H), 1.76 (d, J=12.5 Hz, 2H), 1.68-1.53 (m, 4H), 1.49-1.36 (m, 1H), 1.36-1.21 (m, 2H). LCMS (ES+) m/z 420 (M+1)

Sources & evidence

ORD record: ord-70c6dd5a177c429d9066863f37914e0c
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669361B2

Reaction notes

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