Potassium Phosphate, Tribasic → 1,1-Dimethylethyl N-[(1S)-2-[[2-methoxy-5-(1H-pyrazol-4-yl)-3-pyridinyl]amino]-2-oxo-1-(phenylmethyl)ethyl]carbamate

HRID 1628235Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([NH:10][C:11](=[O:28])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][NH:40][CH:41]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(O)(CC)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:9][O:8][C:5]1[C:4]([NH:10][C:11](=[O:28])[C@@H:12]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:3][C:2]([C:37]2[CH:38]=[N:39][NH:40][CH:41]=2)=[CH:7][N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (S)-tert-butyl 1-(5-bromo-2-methoxypyridin-3-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 15.1.B (1.00 g, 2.22 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole (0.52 g, 2.66 mmol, available from Aldrich) in t-amyl alcohol (20 mL) was added K3PO4 (1.41 g, 6.66 mmol), Pd2(dba)3 (102 mg, 0.111 mmol) and XPhos (212 mg, 0.444 mmol). The mixture was stirred for 4 hours at 100° C. and then was filtered over celite. The organic phase was concentrated and purified by flash chromatography on silica gel to afford tert-butyl (S)-1-(2-methoxy-5-(1H-pyrazol-4-yl)pyridin-3-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 15.1.C.

Workup

filtrationwas filtered over celite
concentrationThe organic phase was concentrated
custompurified by flash chromatography on silica gel

Sources & evidence

ORD record: ord-302ec4a16f374ba9984bd206db408fc7
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785468B2

Reaction notes

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