1-Methyl-1H-imidazol-2-amine → 2,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(1-methyl-1H-imidazol-2-ylamino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamide

HRID 525632노트

반응식

HRID 525632 반응식
Cl[CH2:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]3[O:19]C(C)(C)[N:17]([C:22](=[O:26])[CH:23]([F:25])[F:24])[C@@H:16]3[CH2:27][F:28])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:29][N:30]1[CH:34]=[CH:33][N:32]=[C:31]1[NH2:35]>CN(C)C=O>[F:25][CH:23]([F:24])[C:22]([NH:17][C@H:16]([CH2:27][F:28])[C@H:15]([OH:19])[C:12]1[CH:13]=[CH:14][C:9]([C:6]2[CH:7]=[N:8][C:3]([CH2:2][NH:35][C:31]3[N:30]([CH3:29])[CH:34]=[CH:33][N:32]=3)=[CH:4][CH:5]=2)=[CH:10][CH:11]=1)=[O:26]

참가 물질

4

반응물 2

HCID 5663211-Methyl-1H-imidazol-2-amineHCID 866955331-{(4S,5R)-5-[4-(6-Chloromethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone

생성물 1

HCID 897910372,2-Difluoro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-{6-[(1-methyl-1H-imidazol-2-ylamino)-methyl]-pyridin-3-yl}-phenyl)-ethyl]-acetamide수율 26.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 1-{(4S,5R)-5-[4-(6-chloromethyl -pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone (25 mg, 0.06 mmol) and 1-Methyl-1H-imidazol-2-ylamine (30 mg, 0.3 mmol) in dimethyl formamide (2 ml) is heated at 75° C. for 16 h. The reaction mixture is concentrated to dryness, dissolved in CH2Cl2 (1 ml) and treated with trifluoroacetic acid (0.5 ml) and water (0.1 ml). The mixture is shaken at ambient temperature for 2 hours and then concentrated to dryness. The crude product is purified by preparative HPLC to give the title compound (7 mg): 1H NMR (400 MHz, DMSO-d6) 2.50 (s, 3H), 3.51 (s, 2H), 4.24-4.36 (m, 1.5H), 4.37-4.46 (m, 0.5H), 4.51-4.59 (m, 0.5H), 4.63-4.71 (m, 0.5H), 4.87-4.92 (m, 1H), 5.31 (s, 2H), 6.22 (t, 1H), 7.05-7.10 (m, 2H), 7.40-7.52 (m, 3H), 7.66-7.74 (m, 2H), 8.09-8.16 (m, 1H), 8.86 (s, 1H), 9.63-9.69 (m, 1H). m/z M+H 434.

후처리

  1. concentrationThe reaction mixture is concentrated to dryness
  2. dissolutiondissolved in CH2Cl2 (1 ml)
  3. additiontreated with trifluoroacetic acid (0.5 ml) and water (0.1 ml)
  4. concentrationconcentrated to dryness
  5. customThe crude product is purified by preparative HPLC

출처 및 근거

ORD 기록
ord-7830c3602f7d4e50a1fdf91ad00c132d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340564B2

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