Trifluoroacetic acid → 4-(1-Phenylcyclopropylamino)-6-(3-(piperazin-1-yl)phenylamino)nicotinamide

HRID 513285

반응식

HRID 513285 반응식
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:23]=[C:24]([N:28]2[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]2)[CH:25]=[CH:26][CH:27]=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+].C(O)(C(F)(F)F)=O>O1CCOCC1.C(Cl)Cl.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:27]=[CH:26][CH:25]=[C:24]([N:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[CH:23]=4)[CH:10]=3)[CH2:14][CH2:13]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

참가 물질

9

반응물 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 22330182tert-Butyl 4-(3-aminophenyl)piperazine-1-carboxylateHCID 866645416-Chloro-4-(1-phenylcyclopropylamino)nicotinamide

생성물 1

HCID 569687044-(1-Phenylcyclopropylamino)-6-(3-(piperazin-1-yl)phenylamino)nicotinamide

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

To a mixture of 6-chloro-4-(1-phenylcyclopropylamino)nicotinamide (150 mg, 0.522 mmol) in p-Dioxane (4.5 mL) was added tert-butyl 4-(3-aminophenyl)piperazine-1-carboxylate (174 mg, 0.626 mmol), Pd(OAc)2 (23 mg, 0.104 mmol), BINAP (65 mg, 0.104 mmol) and Cs2CO3 (510 mg, 1.566 mmol). After stirred at 80° C. for 15 h, it was concentrated to give crude residue, which was then treated with TFA in DCM, 30 min later, the solution was concentrated, the residue was purified by preparative HPLC to give 4-(1-phenylcyclopropylamino)-6-(3-(piperazin-1-yl)phenylamino)nicotinamide. MS found for C25H28N6O as (M+H)+ 429.4. UV: λ=254.6 nm. 1H NMR: (CD3OD) δ 8.17 (s, 1H), 7.31-7.20 (m, 4H), 7.13 (m, 2H), 6.95 (dd, J=8.0, 2.0 Hz, 1H), 6.79 (t, J=2.0 Hz, 1H), 6.60 (dd, J=7.2, 2.0 Hz, 1H), 6.12 (s, 1H), 3.34 (m, 8H), 1.36 (m, 4H) ppm.

후처리

  1. concentrationit was concentrated
  2. customto give crude residue, which
  3. concentrationthe solution was concentrated
  4. customthe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-1a1cca8c149e4bdda16d8f9adfe98a25
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102625B2

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