HCID 71143893, compound → HCID 86727267, compound

HRID 2173090Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20](Cl)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:35][N:36]1[C:40]2[S:41][C:42]([Sn](CCCC)(CCCC)CCCC)=[CH:43][C:39]=2[C:38]([CH3:57])=[N:37]1>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:42]2[S:41][C:40]3[N:36]([CH3:35])[N:37]=[C:38]([CH3:57])[C:39]=3[CH:43]=2)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of tert-butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (120 mg, 0.240 mmol), 1,3-dimethyl-5-(tributylstannyl)-1H-thieno[2,3-c]pyrazole (212 mg, 0.481 mmol) and tetrakis(triphenylphosphine)palladium(0) (139 mg, 0.120 mmol) in toluene (3 mL) was heated to 120° C. in a Biotage Initiator microwave for 30 minutes. The mixture was concentrated to give the intermediate, tert-butyl 6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-4-(1,3-dimethyl-1H-thieno[2,3-c]pyrazol-5-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate, which was subsequently dissolved in DCM (5 mL) and TFA (5 mL). The resulting solution was stirred at room temperature for 20 minutes, concentrated, and purified by preparatory HPLC, eluting with a gradient of 10-40% ACN (0.035% TFA) and water (0.05% TFA). The collected fractions were combined and dried to give a TFA salt of the title compound as a white solid (89 mg, 89%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48-1.73 (m, 5H), 1.83-1.97 (m, 3H), 2.35 (s, 3H), 3.78-3.79 (m, 1H), 3.86 (s, 3H), 4.26-4.27 (m, 1H), 4.43 (d, J=4.88 Hz, 2H), 7.02-7.04 (m, 1H), 7.81-7.82 (m, 2H), 8.51 (s, 1H), 9.16 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C20H23FN6OS, 415. found, 415.

Workup

concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-cdbcb6f54e2d4cfcb927b8e4f39bddbf
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056873B2

Reaction notes

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