Potassium Carbonate → HCID 75204435, compound

HRID 1755255Notes

Reaction equation

HRID 1755255 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.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:25][C:26]1[CH:31]=[CH:30][C:29]([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)=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 75204202HCID 75204202, compound

Product 1

HCID 75204435HCID 75204435, compoundYield 37.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 (0.036 g, 0.093 mmol, 1 eq) in 1.8 mL of DMF was added (4-fluorophenyl)boronic acid (0.10 g, 0.71 mmol, 7.7 eq), followed by K2CO3 (0.18 g, 1.3 mmol, 14 eq) in 0.2 mL of H2O and Pd(dppf)Cl2 (0.02 g, 0.03 mmol, 0.3 eq). After heating for 1 h at 120° C. the mixture was filtered and purified by HPLC to afford (S)-5-(4-fluorophenyl)-N-(1-(pyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)pyrimidine-2-carboxamide (0.014 g, 0.035 mmol, 37%). 1H NMR (400 MHz, CD3OD) δ 9.17 (s, 2 H), 7.83 (m, 3 H), 7.71 (d, J=5.4 Hz, 1 H), 7.56 (s, 1 H), 7.31 (t, J=8.5 Hz, 2 H), 6.92 (s, 1 H), 6.85 (d, J=5.9 Hz, 1 H), 5.00-3.60 (br, 5 H), 2.65-2.30 (br, 2 H); MS: (ES) m/z calculated for C22H19FN6O [M+H]+ 403.2, found 403.

Workup

  1. filtrationwas filtered
  2. custompurified by HPLC

Sources & evidence

ORD record
ord-52111d0b8d7f45ca86bb2b47d9090f63
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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