5-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-2(1H)-one → 5-tert-Butyl-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one

HRID 1772099Notes

Reaction equation

HRID 1772099 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][N:14]=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C([O:20][CH2:21][C:22]1[C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=[CH:24][C:23]=1[N:37]1[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[C:42]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:43]=2)[C:38]1=[O:50])(=O)C>>[C:46]([C:42]1[CH:43]=[C:44]2[C:39](=[CH:40][CH:41]=1)[C:38](=[O:50])[N:37]([C:23]1[CH:24]=[CH:25][CH:26]=[C:27]([C:2]3[CH:3]=[C:4]([NH:10][C:11]4[CH:16]=[CH:15][N:14]=[CH:13][N:12]=4)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=3)[C:22]=1[CH2:21][OH:20])[CH2:45]2)([CH3:49])([CH3:47])[CH3:48]

Participants

3

Reactant 2

HCID 580440945-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-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 569284455-tert-Butyl-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-oneYield 38%

Procedure

Using the same general procedure as in Example 105, reaction of 107a (250 mg, 0.889 mmol) with 103f (495 mg, 1.07 mmol) afforded 107 in 38% yield (166 mg) as an amorphous off-white solid: mp 216-218° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.72 (d, J=2.0 Hz, 1H), 8.65 (s, 1H), 8.30 (d, J=5.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 2H), 7.62 (dd, J=8.0, 1.5 Hz, 1H), 7.54 (d, J=2.0 Hz, 1H), 7.51 (t, J=7.5 Hz, 1H), 7.46 (dd, J=7.5, 1.0 Hz, 1H), 7.40 (dd, J=7.5, 1.5 Hz, 1H), 7.32 (dd, J=6.0, 1.0 Hz, 1H), 4.95 (s, 2H), 4.92 (t, J=4.5 Hz, 1H), 4.34 (d, J=5.0 Hz, 2H), 3.61 (s, 3H), 1.37 (s, 9H); MS (ESI+) m/z 496.2 (M+H).

Sources & evidence

ORD record
ord-b82d9bf7364048308af6697c271a025c
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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