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Aniline → 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(phenylamino)pyrazine-2-carbonitrile

HRID 2200433
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HRID 2200433 반응식
[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13](Cl)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].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>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1
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참가 물질

7

반응물 4

HCID 6115AnilineHCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 866855565-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile

생성물 1

HCID 866855645-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(phenylamino)pyrazine-2-carbonitrile수율 53.1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매
HCID 312751,4-Dioxane용매

실험 절차

A mixture of 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile (74 mg, 0.257 mmol), aniline (0.040 mL, 0.439 mmol), K2CO3 (80 mg, 0.579 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (10 mg, 0.044 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 3 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(phenylamino)pyrazine-2-carbonitrile (47 mg).

후처리

  1. customwas degassed with Ar
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-d48158d3e8aa4ed099c0be61498fe860
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09359308B2

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