1-Ethyl-1H-pyrazole-4-boronic acid, pinacol ester → HCID 71143916, compound

HRID 2173092Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20](Cl)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:35]([N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1)[CH3:36]>O1CCOCC1.C([O-])(O)=O.[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:40]3[CH:39]=[N:38][N:37]([CH2:35][CH3:36])[CH:41]=3)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of bis(triphenylphosphine)palladium chloride (14.01 mg, 0.020 mmol), tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (200 mg, 0.399 mmol), and 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (177 mg, 0.798 mmol) in dioxane (4 mL) and saturated aqueous NaHCO3 (1 mL) was heated to 100° C. in a Biotage Initiator microwave for 1 hour. The mixture was concentrated to give the intermediate, tert-butyl 6-(((3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl)amino)-4-(1-ethyl-1H-pyrazol-4-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 10-25% 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 (87 mg, 60%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40 (t, J=7.3 Hz, 3H), 1.75-1.77 (m, 1H), 2.10-2.11 (m, 1H), 3.61-3.63 (m, 1H), 3.85-3.86 (m, 1H), 3.93-3.94 (m, 1H), 3.96-3.98 (m, 2H), 4.18 (q, J=7.32, 2H), 4.47-4.48 (m, 1H), 7.04-7.05 (m, 1H), 7.89-7.91 (m, 2H), 8.30 (s, 1H), 8.37 (s, 1H), 8.88 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C17H21FN6O2, 361. found, 361.

Workup

concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-5459f9d2bbfd43ba95c51c6561a03961
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056873B2

Reaction notes

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