Hydrochloric Acid → 3-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamide

HRID 577420노트

반응식

HRID 577420 반응식
CS[C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.CCN(C(C)C)C(C)C.Cl.Cl.[F:47][C:48]1([F:56])[CH2:53][CH2:52][CH2:51][C@@H:50]([NH2:54])[C@H:49]1[NH2:55].C(O)(C(F)(F)F)=O.Cl>CN1C(=O)CCC1>[NH2:55][C@H:49]1[C:48]([F:56])([F:47])[CH2:53][CH2:52][CH2:51][C@H:50]1[NH:54][C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1

참가 물질

8

반응물 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 81531DiisopropylethylamineHCID 86685557(1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochlorideHCID 867064133-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide

생성물 1

HCID 727032273-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamide수율 66.1%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

3-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide (40 mg, 0.12 mmol) was dissolved in 4 mL NMP. To it was added mCPBA (77%) (108 mg, 0.48 mmol). The mixture was stirred at RT for 1 h. To it was added DIEA (0.21 mL, 1.20 mmol) and (1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochloride (53 mg, 0.24 mmol). The mixture was stirred at 80° C. for 1 h. It was cooled to RT, acidified with TFA (0.3 mL) and subjected to reverse phase preparative HPLC to isolate the title compound (35 mg) as HCl salt. MS found for C20H21F2N9O as (M+H)+ 442.5. UV: λ=240 nm. Proton NMR: (CD3OD) δ 8.94-8.92 (3H, m), 8.41 (1H, d, J=8.0 Hz), 7.79 (1H, d, J=8.0 Hz), 7.64 (1H, t, J=8.0 Hz), 7.45 (1H, t, J=4.8 Hz), 4.90 (1H, m), 4.13 (1H, m), 2.24-1.82 (6H, m) ppm.

후처리

  1. stirringThe mixture was stirred at 80° C. for 1 h
  2. temperatureIt was cooled to RT

출처 및 근거

ORD 기록
ord-401d987570874833b73dd58a3b875d23
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040530B2

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