2-Fluoro-4-(cyclopropyl)phenylboronic acid pinacol ester → (R)-5-amino-N-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(4-cyclopropyl-2-fluorophenyl)thiazole-4-carboxamide

HRID 2089353Notes

Reaction equation

HRID 2089353 reaction equation
C(OC(=O)[NH:10][C@@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[N:19]([CH3:40])[N:20]=[CH:21][C:22]=2[NH:23][C:24]([C:26]2[N:27]=[C:28](Br)[S:29][C:30]=2[NH:31]C(OC(C)(C)C)=O)=[O:25])[CH2:13][CH2:12]1)C1C=CC=CC=1.[CH:42]1([C:45]2[CH:50]=[CH:49][C:48](B3OC(C)(C)C(C)(C)O3)=[C:47]([F:60])[CH:46]=2)[CH2:44][CH2:43]1>>[NH2:31][C:30]1[S:29][C:28]([C:48]2[CH:49]=[CH:50][C:45]([CH:42]3[CH2:44][CH2:43]3)=[CH:46][C:47]=2[F:60])=[N:27][C:26]=1[C:24]([NH:23][C:22]1[CH:21]=[N:20][N:19]([CH3:40])[C:18]=1[N:14]1[CH2:15][CH2:16][CH2:17][C@@H:11]([NH2:10])[CH2:12][CH2:13]1)=[O:25]

Participants

3

Reactant 2

HCID 584648422-Fluoro-4-(cyclopropyl)phenylboronic acid pinacol esterHCID 58464869((R)-1-{4-[(2-Bromo-5-tert-butoxycarbonylamino-thiazole-4-carbonyl)-amino]-2-methyl-2H-pyrazol-3-yl}-perhydro-azepin-4-yl)-carbamic acid benzyl ester

Product 1

HCID 58464863(R)-5-amino-N-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(4-cyclopropyl-2-fluorophenyl)thiazole-4-carboxamideYield 37.8%

Procedure

Following the procedures from Example 210 and shown in FIG. 3, using ((R)-1-{4-[(2-bromo-5-tert-butoxycarbonylamino-thiazole-4-carbonyl)-amino]-2-methyl-2H-pyrazol-3-yl}-perhydro-azepin-4-yl)-carbamic acid benzyl ester and 2-(4-cyclopropyl-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as starting materials, 222 was obtained in 37.8% yield over two steps: 1H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 8.10 (t, J=8.2 Hz, 1H), 7.53 (s, 1H), 7.35 (s, 2H), 7.06 (dd, J=19.7, 10.7 Hz, 2H), 3.65 (s, 3H), 3.21-2.99 (m, 5H), 2.05-1.95 (m, 1H), 1.90-1.73 (m, 4H), 1.65-1.47 (m, 3H), 1.06-0.99 (m, 2H), 0.81-0.75 (m, 2H); MS (ESI) m/z: 470.2 [M+H]+

Workup

  1. custom222 was obtained in 37.8% yield over two steps

Sources & evidence

ORD record
ord-a2deac40b9cd4c2198d03560bf33f518
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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