Phosphate → N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

HRID 510212Notes

Reaction equation

HRID 510212 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=3)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]2=[N:6][CH:7]=1.[CH3:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:38][N:39]1[CH:43]=[C:42]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]4[CH:12]=[C:13]([NH:17][C@H:18]([C:22]([NH:24][CH2:25][C:26]([F:27])([F:28])[F:29])=[O:23])[CH:19]([CH3:21])[CH3:20])[CH:14]=[N:15][CH:16]=4)=[CH:9][N:8]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:5]3=[N:6][CH:7]=2)[CH:41]=[N:40]1

Participants

8

Reactant 4

HCID 1061PhosphateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 131733258N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide

Product 1

HCID 131733262N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N2-[5-(5-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide 2-1a (200 mg, 0.360 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (CA) (90 mg, 0.432 mmol), X-PHOS (30.9 mg, 0.065 mmol), palladium(II) acetate (9.69 mg, 0.043 mmol) in DMF (2 mL) was added phosphate tribasic (153 mg, 0.719 mmol) and water (0.4 mL). The mixture was evacuated then N2 purged 3 times and heated at 100° C. for overnight. After cooling the reaction was filtered and filtrate was loaded directly onto HPLC Reverse phase (C-18), eluting with acetonitrile/water (0.1% TFA), to give product 8-1a as a colorless foam. MS APCI: [M+H]+ m/z=602.1.

Workup

  1. customThe mixture was evacuated
  2. customN2 purged 3 times
  3. temperatureAfter cooling the reaction
  4. filtrationwas filtered
  5. washeluting with acetonitrile/water (0.1% TFA)

Sources & evidence

ORD record
ord-6fecbb097ea84b67a7244eeb37fa0194
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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