Diisopropylethylamine → N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

HRID 6884

반응식

HRID 6884 반응식
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][CH2:12][C:13]1[S:17][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[N:15][CH:14]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:49][C:50]([F:55])([CH2:53][NH2:54])[CH2:51][NH2:52].CCN(C(C)C)C(C)C>CN(C=O)C.C1COCC1.C(Cl)Cl>[NH2:52][CH2:51][C:50]([F:55])([F:49])[CH2:53][NH:54][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([NH:11][CH2:12][C:13]2[S:17][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[N:15][CH:14]=2)[CH:4]=1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 199026522,2-Difluoropropane-1,3-diamineHCID 220190564-Fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid2회

생성물 1

HCID 22019140N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide수율 65%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a mixture of 4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid (compound 52A, 21 mg, 0.06 mmol) and HATU (38 mg, 0.1 mmol) in DMF (0.2 ml) and THF (0.4 ml), were added 2,2-difluoro-1,3-propanediamine (ref. Tetrahedron, 8617, 1994) (60 mg, 0.54 mmol) and DIPEA (26 mg, 0.2 mmol). The resulting mixture was stirred at RT for 18 h, then diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc] to afford the title compound (17 mg, 65%) as a white solid. LC/MS; (M+H)+=437.

후처리

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc]

출처 및 근거

ORD 기록
ord-998102171ea145578b3da40483685ff2
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07084160B2

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