Water → (1R,2R)-2-((6-((5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

HRID 1848171ノート

反応式

HRID 1848171 の反応式
[CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]2[N:7]([CH2:10][C:11]3[CH:22]=[CH:21][C:14]4[N:15]=[C:16](S(C)=O)[O:17][C:13]=4[CH:12]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[OH:32].CCN(C(C)C)C(C)C.O>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]2[N:7]([CH2:10][C:11]3[CH:22]=[CH:21][C:14]4[N:15]=[C:16]([NH:25][C@@H:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]5[OH:32])[O:17][C:13]=4[CH:12]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 866811406-((5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

生成物 1

HCID 86681141(1R,2R)-2-((6-((5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol収率 29.9%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of 6-((5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole (450 mg, 1.32 mmol), (1R,2R)-2-aminocyclohexanol (228 mg, 1.98 mmol) and DIEA (341 mg, 2.64 mmol) in DMA (10 mL) was stirred at 120° C. for 1.5 h. The reaction mixture was cooled to rt and poured into water (30 mL) and the resulting mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to give (1R,2R)-2-((6-((5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol as a white solid (155 mg, 29.9%). 1H NMR (300 MHz, DMSO-d6) δ 8.32 (s, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.41 (d, J=8.7 Hz, 1H), 7.33 (s, 1H), 7.16-7.08 (m, 3H), 6.82 (dd, J=2.4, 8.7 Hz, 1H), 5.42 (s, 2H), 4.68 (d, J=4.5 Hz, 1H), 3.75 (s, 3H), 3.35 (br s, 2H), 1.90 (m, 2H), 1.62 (br s, 2H), 1.22 (br s, 4H). LCMS (ESI) m/z 393 (M+H)+.

後処理

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionthe resulting mixture was extracted with ethyl acetate (30 mL×3)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-aac8b9232131438b8f74d577074ba463
出典データセット
uspto-grants-2015_02
特許番号
US08952058B2

反応ノート

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