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

HRID 1772113Notes

Reaction equation

HRID 1772113 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[N:9]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[CH:26]=[C:25]([NH:27][C:28]4[CH:32]=[C:31]([CH3:33])N(C)[N:29]=4)[C:24](=[O:35])[N:23]([CH3:36])[CH:22]=3)[C:16]=1[CH2:37][OH:38])[CH2:8]2)([CH3:4])([CH3:3])[CH3:2].[C:39](OCC1C(B2OC(C)(C)C(C)(C)O2)=CC=CC=1N1CC2C(=CC=C(C(C)(C)C)C=2)C1=O)(=O)C.BrC1C=C(NC2C=CC=CN=2)C(=O)N(C)C=1>>[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[N:9]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[CH:26]=[C:25]([NH:27][C:28]4[CH:32]=[CH:31][CH:33]=[CH:39][N:29]=4)[C:24](=[O:35])[N:23]([CH3:36])[CH:22]=3)[C:16]=1[CH2:37][OH:38])[CH2:8]2)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 3

HCID 569284435-tert-Butyl-2-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(hydroxymethyl)phenyl)isoindolin-1-oneHCID 665987735-Bromo-1-methyl-3-(pyridin-2-ylamino)-1h-pyridin-2-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 569285525-tert-Butyl-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyridin-2-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-oneYield 34%

Procedure

Using the same general procedure as described for the preparation of 105, reaction 103f (298 mg, 0.643 mmol) with 113a (150 mg, 0.536 mmol) gave a 34% yield (90 mg) of 113 as a white solid: mp 138-139° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.68 (d, 1H, J=2.0 Hz), 8.58 (s, 1H), 8.17 (m, 1H), 7.73-7.71 (m, 2H), 7.62-7.56 (m, 2H), 7.50 (t, 1H, J=7.5 Hz), 7.44 (d, 1H, J=7.5 Hz), 7.39-7.37 (m, 2H), 7.28 (d, 1H, J=7.5 Hz), 6.78 (dd, 1H, J=6.5, 5.0 Hz), 4.94 (s, 2H), 4.89 (t, 1H, J=4.5 Hz), 4.34 (d, 2H, J=4.5 Hz), 3.60 (s, 3H), 1.65 (s, 9H); MS (ESI+) m/z 495.2 (M+H).

Sources & evidence

ORD record
ord-41f5a2facb9743bbacfefa9307a069a1
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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