Water → 2-[(2S)-2-[3-(4-Chloro-1-methyl-1H-pyrazol-5-yl)-7-oxo-5,7-dihydro-6H-pyrrolo [3,4-b]pyridin-6-yl]-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione

HRID 339985Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1B1OC(C)(C)C(C)(C)O1.Br[C:18]1[CH:19]=[C:20]2[CH2:26][N:25]([C@@H:27]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[CH:42]=3)[CH2:28][N:29]3[C:37](=[O:38])[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:30]3=[O:39])[C:24](=[O:48])[C:21]2=[N:22][CH:23]=1.C(N(CC)C(C)C)(C)C.O1CCOCC1.O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:18]1[CH:19]=[C:20]2[CH2:26][N:25]([C@@H:27]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[CH:42]=3)[CH2:28][N:29]3[C:37](=[O:38])[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:30]3=[O:39])[C:24](=[O:48])[C:21]2=[N:22][CH:23]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (150 mg, 0.63 mmol), 2-[(2S)-2-(3-bromo-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (150 mg, 0.32 mmol), bis(tri-t-butylphosphine)palladium (30 mg, 0.06 mmol) and N,N-diisopropylethylamine (0.16 mL, 0.95 mmol) in 1,4-dioxane (5.0 mL, 64 mmol) and water (0.5 mL, 30 mmol) was stirred at 110° C. for 40 min at microwave. Direct purification on prep.—HPLC (pH=10) afforded 48 mg (29% yield) of the desired intermediate as white solid. LC-MS found: 530.1 (M+H)+.

Workup

customDirect purification on prep.—HPLC (pH=10)

Sources & evidence

ORD record: ord-d07f48428a0646cfa5df0c81ace31ba9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895571B2

Reaction notes

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