Cesium carbonate → 4-(1-Phenylcyclopropylamino)-6-(4-(4-propionylpiperazin-1-yl)phenylamino)nicotinamide

HRID 513273Notes

Reaction equation

Cl[C:2]1[CH:10]=[C:9]([NH:11][C:12]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:14][CH2:13]2)[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:34](=[O:37])[CH2:35][CH3:36])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:15]1([C:12]2([NH:11][C:9]3[C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=[C:2]([NH:21][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:29][CH2:30][N:31]([C:34](=[O:37])[CH2:35][CH3:36])[CH2:32][CH2:33]5)=[CH:26][CH:27]=4)[CH:10]=3)[CH2:14][CH2:13]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-4-(1-phenylcyclopropylamino)nicotinamide (50 mg, 0.174 mmol) in dioxane (1 mL) was added 1-(4-(4-aminophenyl)piperazin-1-yl)propan-1-one (61 mg, 0.261 mmol), BINAP (22 mg, 0.035 mmol), Pd(OAc)2 (8 mg, 0.035 mmol) and Cs2CO3 (170 mg, 0.52 mmol). After degassed with Argon, the mixture was heated at 80° C. for 15 h. The mixture was diluted with dioxane, precipitate was filtered off, filter cake was washed with AcCN, the filtrate was concentrated and purified by preparative HPLC to give of 4-(1-phenylcyclopropylamino)-6-(4-(4-propionylpiperazin-1-yl)phenylamino)nicotinamide (16 mg). MS found for C28H32N6O2 as (M+H)+ 485.5. λ=258.2.

Workup

customAfter degassed with Argon
additionThe mixture was diluted with dioxane, precipitate
filtrationwas filtered off
filtrationfilter cake
washwas washed with AcCN
concentrationthe filtrate was concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-cb4b8f6e590c4cc29ddb94d837a7f46b
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102625B2

Reaction notes

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