Bromide ion → HCID 22669094, 화합물

HRID 1007529노트

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HRID 1007529 반응식
[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

참가 물질

7

반응물 4

HCID 259Bromide ionHCID 696322-BromoacetamideHCID 516892Sodium Bicarbonate2회HCID 178518612HCID 178518612, 화합물

생성물 1

HCID 22669094HCID 22669094, 화합물수율 19.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-2f3969f58390430dbecf695cb007ce30
출처 데이터셋
uspto-grants-2004_09
특허 번호
US06794402B2

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