Dichloromethane → (2S)-N-(cyanomethyl)-4-methyl-2-{phenyl[5-(4-piperazin-1-ylphenyl)pyridin-2-yl]methoxy}pentanamide

HRID 1180438Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C@@H:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:11]([NH:13][CH2:14][C:15]#[N:16])=[O:12])=[N:6][CH:7]=1.[N:27]1([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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]>[C:15]([CH2:14][NH:13][C:11](=[O:12])[C@@H:10]([O:9][CH:8]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:5]1[CH:4]=[CH:3][C:2]([C:36]2[CH:35]=[CH:34][C:33]([N:27]3[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]3)=[CH:38][CH:37]=2)=[CH:7][N:6]=1)[CH2:17][CH:18]([CH3:20])[CH3:19])#[N:16]

Participants

Conditions

Temperature: 90 °C

Procedure

(2S)-2-[(5-bromopyridin-2-yl)(phenyl)methoxy]-N-(cyanomethyl)-4-methylpentanamide from example 53 step 3 (156 mg, 0.375 mmol), 4-piperazine-1-ylphenyl boronic acid (100 mg, 0.413 mmol, 1.1 eg), [1,1′-Bis(diphenylphosphino)-ferrocene dichloropalladium II complex with CH2Cl2 (13.7 mg, 0.0187 mmol, 0.05 eg), sodium carbonate (2M soln, 750 uL, 1.5 mmol, 4 eg) were mixed together in DMF (5 mL). The reaction mixture was degased 3× with N2, then heated to 90° C. for 5 hours. After cooling, the mixture was evaporated under high vacuum and residue was chromatographed with a mixture of dichloromethane/methanol/ammonium hydroxide (90:9:1) to give the title compound.

Workup

customThe reaction mixture was degased 3× with N2
temperatureAfter cooling
customthe mixture was evaporated under high vacuum and residue
customwas chromatographed with a mixture of dichloromethane/methanol/ammonium hydroxide (90:9:1)

Sources & evidence

ORD record: ord-30ef33e6592f416d83a33151d253d1ae
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07279478B2

Reaction notes

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