Water → HCID 59333980, compound

HRID 1927012Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14]2[C:13]([NH:16][C:17]3[C:22]([F:23])=[CH:21][N:20]=[C:19](Cl)[N:18]=3)=[N:12][NH:11][C:10]=2[C:9]1([CH3:26])[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C1COCC1>[F:23][C:22]1[C:17]([NH:16][C:13]2[C:14]3[CH2:15][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:9]([CH3:26])([CH3:25])[C:10]=3[NH:11][N:12]=2)=[N:18][C:19]([CH3:27])=[N:20][CH:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a pressure vessel was added 3-(2-Chloro-5-fluoro-pyrimidin-4-ylamino)-6,6-dimethyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester (1.50 g, 3.90 mmol), trimethylboroxine (10.9 mL, 78.4 mmol), cesium carbonate (25.5 g, 78.4 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.480 g, 0.588 mmol), H2O (6 mL), and THF (60 mL). The suspension was purged with argon for 2 min, then heat at 100° C. for 15 h. The cooled solution was filtered to remove undissolved solids. Purification by silica gel column chromatography using 0-10% ammoniated methanol in CH2Cl2 provided the desired product H1(i) as a brown solid (0.80 g, 56%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.41 (s, 9H) 1.57 (s, 6H) 2.38 (s, 3H) 4.43-4.58 (m, 2H) 8.12 (s, 1H) 10.02 (s, 1H) 12.34 (s, 1H). Mass Spectrum: Calcd for C17H24N6O2F (M+H): 363. Found: 363.

Workup

customThe suspension was purged with argon for 2 min
filtrationThe cooled solution was filtered
customto remove undissolved solids
customPurification by silica gel column chromatography

Sources & evidence

ORD record: ord-cffb67675ce941a9925232f62f3be8c5
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183255B2

Reaction notes

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