Potassium Carbonate → 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(isoxazol-5-yl)phenylamino)pyrazine-2-carbonitrile

HRID 332760노트

반응식

HRID 332760 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.[O:20]1[C:24]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)=[CH:23][CH:22]=[N:21]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:29][C:28]2[CH:27]=[CH:26][C:25]([C:24]3[O:20][N:21]=[CH:22][CH:23]=3)=[CH:31][CH:30]=2)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 170248234-(1,2-Oxazol-5-yl)anilineHCID 866855565-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile

생성물 1

HCID 866855665-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(isoxazol-5-yl)phenylamino)pyrazine-2-carbonitrile수율 3.8%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 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), 4-(isoxazol-5-yl)aniline (60 mg, 0.375 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 20 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(isoxazol-5-yl)phenylamino)pyrazine-2-carbonitrile (4 mg). The compound 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(4-(isoxazol-5-yl)phenylamino)pyrazine-2-carbonitrile (4 mg, 0.010 mmol) was dissolved in EtOH (1 mL) and DMSO (0.5 mL), aq. 1N NaOH (0.50 mL) and aq. H2O2 (30%, 0.50 mL) were added. The mixture was stirred at room temperature for 60 min. HOAc (0.25 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (3 mg). MS 430.4 (M+H); UV 202.3, 234.0, 274.4, 331.8 nm; t 0.483 min.

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-1cc9855ac51941a4b6d5ddc9b50999da
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877760B2

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