Potassium Phosphate, Tribasic → HCID 75204434, compound

HRID 1755254Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([C:8]([NH:10][C@H:11]2[CH2:15][CH2:14][N:13]([C:16]3[C:17]4[N:18]([CH:22]=[CH:23][CH:24]=4)[CH:19]=[CH:20][N:21]=3)[CH2:12]2)=[O:9])=[N:6][CH:7]=1.[CH:25]1(B2OC(C)(C)C(C)(C)O2)[CH2:27][CH2:26]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:25]1([C:2]2[CH:3]=[N:4][C:5]([C:8]([NH:10][C@H:11]3[CH2:15][CH2:14][N:13]([C:16]4[C:17]5[N:18]([CH:22]=[CH:23][CH:24]=5)[CH:19]=[CH:20][N:21]=4)[CH2:12]3)=[O:9])=[N:6][CH:7]=2)[CH2:27][CH2:26]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (S)-5-bromo-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)pyrimidine-2-carboxamide (0.25 g, 0.65 mmol, 1 eq) in 2 mL of toluene was added 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.16 g, 1.86 mmol, 2.8 eq), followed by PCy3 (0.033 g, 0.11 mmol, 0.2 eq), K3PO4 (0.48 g, 2.3 mmol, 3.5 eq) in 0.1 mL of H2O and Pd(OAc)2 (0.013 g, 0.06 mmol, 0.1 eq). After heating for 1 h at 120° C. the mixture was filtered and purified by HPLC to afford (S)-5-cyclopropyl-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)pyrimidine-2-carboxamide (0.009 g, 0.026 mmol, 4%). 1H NMR (400 MHz, CD3OD) δ 8.64 (s, 2 H), 7.76 (m, 1 H), 7.71 (d, J=5.4 Hz, 1 H), 7.54 (s, 1 H), 6.92 (dd, J=2.6, 4.4 Hz, 1 H), 6.84 (d, J=5.5 Hz, 1 H), 5.00-3.60 (br, 5 H), 2.65-2.30 (br, 2 H), 2.07-2.02 (m, 1 H), 1.23-1.18 (m, 2 H), 0.96-0.91 (m, 2 H); MS: (ES) m/z calculated for C19H20N6O [M+H]+ 349.2, found 349.

Workup

filtrationwas filtered
custompurified by HPLC

Sources & evidence

ORD record: ord-cf7286f3f3934c868658461fd3cba8c0
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169261B2

Reaction notes

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