Bromide ion → HCID 22669094、化合物

HRID 1007529ノート

反応式

HRID 1007529 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].Br[CH2:34][C:35]([NH2:37])=[O:36].[Br-]>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]([CH:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14][CH2:13]2)[CH2:34][C:35]([NH2:37])=[O:36])=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 259Bromide ionHCID 696322-BromoacetamideHCID 516892Sodium Bicarbonate2 回HCID 178518612HCID 178518612、化合物

生成物 1

HCID 22669094HCID 22669094、化合物収率 19.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

To a stirred suspension of 6-{trans-4-[3-(4-fluorophenyl)propylamino]-cyclohexyl}-3H-benzoxazol-2-one (110 mg, 0.81 mmol) in DMF (15 mL) was added NaHCO3 (140 mg, 1.6 mmol) and bromoacetamide (300 mg, 0.74 mmol). After 16 hours the reaction mixture was warmed to 50° C. After 4 hours, additional bromide (150 mg, 0.37 mmol) and NaHCO3 (31 mg, 0.37 mmol) were added, and the temperature was increased to 75° C. After 4 hours, the reaction mixture was cooled to room temperature, diluted with water and extracted with EtOAc. The combined organics were washed with water, saturated NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 95:4.75:0.25 CH2Cl2:MeOH:NH4OH) followed by conversion to the HCl salt gave compound 2-{[3-(4-fluorophenyl)propyl]-[4-(2-oxo-2,3-dihydro-benzoxazol-6-yl)-cyclohexyl]amino}acetamide (60 mg, 17%), as a white solid: mp 266-270° C.; IR (KBr): 3331, 3149, 2943, 1762, 1691 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.47 (s, 1H), 9.08 (br s, 1H), 7.96 (br s, 1H), 7.73 (br s, 1H), 7.29-7.25 (m, 2H), 7.17-7.01 (m, 3H), 6.99 (s, 2H), 4.05-4.02 (m, 1H), 3.81-3.78 (m, 1H), 3.47-3.38 (m, 1H), 3.22-3.12 (m, 3H), 2.63 (t, J=8 Hz, 2H), 2.57-2.52 (m, 1H), 2.14-1.87 (m, 6H), 1.71-1.49 (m, 4H); ESI-MS (m/z): 426 [M+H]+; HPLC: method A, 5.44 minutes (98.0%); HPLC: method E, 6.50 minutes (>99%); Anal. Calcd for C24H28FN3O3.HCl: C, 61.80; H, 6.37; N, 9.01. Found: C, 61.78; H, 6.27; N, 8.80.

後処理

  1. temperaturethe temperature was increased to 75° C
  2. waitAfter 4 hours
  3. temperaturethe reaction mixture was cooled to room temperature
  4. extractionextracted with EtOAc
  5. washThe combined organics were washed with water, saturated NaCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash chromatography (silica, 95:4.75:0.25 CH2Cl2:MeOH:NH4OH)

出典と根拠

ORDレコード
ord-2f3969f58390430dbecf695cb007ce30
出典データセット
uspto-grants-2004_09
特許番号
US06794402B2

反応ノート

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