5-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-one → 5-tert-Butyl-2-(3-(6-(1-cyclopropyl-1H-pyrazol-4-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-(hydroxymethyl)phenyl)isoindolin-1-one

HRID 1772105Notes

Reaction equation

HRID 1772105 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[N:13][N:14]([CH:16]3[CH2:18][CH2:17]3)[CH:15]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C([O:22][CH2:23][C:24]1[C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=[CH:26][C:25]=1[N:39]1[CH2:47][C:46]2[C:41](=[CH:42][CH:43]=[C:44]([C:48]([CH3:51])([CH3:50])[CH3:49])[CH:45]=2)[C:40]1=[O:52])(=O)C>>[C:48]([C:44]1[CH:45]=[C:46]2[C:41](=[CH:42][CH:43]=1)[C:40](=[O:52])[N:39]([C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([C:2]3[N:3]=[C:4]([NH:10][C:11]4[CH:12]=[N:13][N:14]([CH:16]5[CH2:18][CH2:17]5)[CH:15]=4)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=3)[C:24]=1[CH2:23][OH:22])[CH2:47]2)([CH3:51])([CH3:49])[CH3:50]

Participants

3

Reactant 2

HCID 580442185-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-oneHCID 866979362-(5-tert-Butyl-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

Product 1

HCID 866998625-tert-Butyl-2-(3-(6-(1-cyclopropyl-1H-pyrazol-4-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-(hydroxymethyl)phenyl)isoindolin-1-oneYield 35.1%

Procedure

Using the same general procedure as Example 105, reaction of 109c (310 mg, 1.00 mmol) and 103f (536 mg, 1.20 mmol) afforded a 35% yield (184 mg) of 109 as an off-white solid: mp 218-219° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.58 (s, 1H), 8.20 (s, 1H), 7.73 (m, 3H), 7.61 (m, 2H), 7.51 (t, 1H, J=7.9 Hz), 7.43 (m, 1H), 7.31 (s, 1H), 4.95 (s, 2H), 4.90 (t, 1H, J=5.0 Hz), 4.48 (d, 2H, J=5.0 Hz), 3.64 (m, 1H), 3.52 (s, 3H), 1.37 (s, 9H), 0.93 (m, 4H); MS (ESI+) m/z 525.2 (M+H).

Sources & evidence

ORD record
ord-f9eafbfaa8544883acc5dd891ac6bf4f
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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