5-tert-Butyl-2-(2-(hydroxymethyl)-3-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one → 5-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one

HRID 1772152Notes

Reaction equation

HRID 1772152 reaction equation
C([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:37]=[C:31]5[CH2:32][N:33]([CH3:36])[CH2:34][CH2:35][N:30]5[N:29]=4)[C:24](=[O:38])[N:23]([CH3:39])[CH:22]=3)[C:16]=1[CH2:40][OH:41])[CH2:8]2)(C)(C)C.C(OCC1C(B2OC(C)(C)C(C)(C)O2)=CC=C[C:48]=1[N:62]1CC2C(=CC=C(N(C)C)C=2)[C:63]1=O)(=O)C>>[CH3:48][N:62]([CH3:63])[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:37]=[C:31]5[CH2:32][N:33]([CH3:36])[CH2:34][CH2:35][N:30]5[N:29]=4)[C:24](=[O:38])[N:23]([CH3:39])[CH:22]=3)[C:16]=1[CH2:40][OH:41])[CH2:8]2

Participants

3

Reactant 2

HCID 569283425-tert-Butyl-2-(2-(hydroxymethyl)-3-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-oneHCID 866998722-(5-(Dimethylamino)-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

Product 1

HCID 569288595-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-oneYield 24%

Procedure

Using the same general procedure as described for the preparation of 103 reaction of 123e (450 mg, 1.00 mmol) with 103l (260 mg, 0.800 mmol) followed by a hydrolysis gave a 24% yield (130 mg) of 123 as a white solid: mp 148-150° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.98 (d, 1H, J=2.0 Hz), 7.56 (d, 1H, J=8.0 Hz), 7.47 (t, 1H, J=8.0 Hz), 7.39 (dd, 1H, J=8.0, 1.5 Hz), 7.33 (dd, 1H, J=8.0, 1.5 Hz), 7.24 (d, 1H, J=2.0 Hz), 6.88-6.85 (m, 2H), 5.88 (s, 1H), 4.89 (t, 1H, J=5.0 Hz), 4.85 (s, 2H), 4.31 (d, 2H, J=5.0 Hz), 3.91 (t, 2H, J=5.5 Hz), 3.59 (s, 3H), 3.48 (s, 2H), 3.04 (s, 6H), 2.77 (t, 2H, J=5.5 Hz), 2.34 (s, 3H); MS (ESI+) m/z 540.3 (M+H).

Sources & evidence

ORD record
ord-f4217e516f1c41ac8e7001d7b30fe4f6
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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