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 1487570ノート

反応式

HRID 1487570 の反応式
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]

参加物

4

反応物 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

生成物 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]-acetamide収率 26.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3744e3aa37ad4de59201133d373877e2
出典データセット
uspto-grants-2016_08
特許番号
US09428528B2

反応ノート

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