5-Bromo-1-methyl-3-(4-morpholinophenylamino)pyrazin-2(1H)-one → 5-tert-Butyl-2-(2-(hydroxymethyl)-3-(4-methyl-6-(4-morpholinophenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)isoindolin-1-one

HRID 1772101Notes

Reaction equation

HRID 1772101 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C([O:26][CH2:27][C:28]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=[CH:30][C:29]=1[N:43]1[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[C:48]([C:52]([CH3:55])([CH3:54])[CH3:53])[CH:49]=2)[C:44]1=[O:56])(=O)C>>[C:52]([C:48]1[CH:49]=[C:50]2[C:45](=[CH:46][CH:47]=1)[C:44](=[O:56])[N:43]([C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([C:2]3[N:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=3)[C:28]=1[CH2:27][OH:26])[CH2:51]2)([CH3:55])([CH3:53])[CH3:54]

Participants

3

Reactant 2

HCID 666134025-Bromo-1-methyl-3-(4-morpholinophenylamino)pyrazin-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 569284465-tert-Butyl-2-(2-(hydroxymethyl)-3-(4-methyl-6-(4-morpholinophenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)isoindolin-1-oneYield 47%

Procedure

Using the same general procedure as Example 105, reaction of 108a (296 mg, 0.810 mmol) with 103f (413 mg, 0.891 mmol) afforded 108 in 47% yield (205 mg) as an amorphous yellow solid: mp 225-227° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 7.83 (d, J=9.0 Hz, 2H), 7.73 (d, J=8.5 Hz, 2H), 7.62 (dd, J=8.0, 1.5 Hz, 1H), 7.58 (dd, J=8.0, 1.5 Hz, 1H), 7.50 (t, J=7.5 Hz, 1H), 7.42 (dd, J=8.0, 1.0 Hz, 1H), 7.34 (s, 1H), 6.89 (d, J=9.0 Hz, 2H), 4.92 (s, 2H), 4.83 (t, J=5.0 Hz, 1H), 4.43 (d, J=5.0 Hz, 2H), 3.72 (t, J=5.5 Hz, 4H), 3.54 (s, 3H), 3.03 (t, J=5.5 Hz, 4H), 1.37 (s, 9H); MS (ESI+) m/z 580.3 (M+H).

Sources & evidence

ORD record
ord-06856c405daa4abd9c9241da87cbf0ac
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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