Dimethylamine → HCID 11756245, 화합물

HRID 346885

반응식

HRID 346885 반응식
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:35])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH2:31][CH:32]3[CH2:34][CH2:33]3)[CH:21]=1)[CH2:16][C:17](O)=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2].[C:36](N1C=CN=C1)([N:38]1C=CN=[CH:39]1)=O.CNC.O>O1CCCC1>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:35])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[C:22]([O:30][CH2:31][CH:32]3[CH2:34][CH2:33]3)[CH:21]=1)[CH2:16][C:17]([N:38]([CH3:39])[CH3:36])=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2]

참가 물질

6

반응물 4

HCID 674DimethylamineHCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 98483373-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid

생성물 1

HCID 11756245HCID 11756245, 화합물수율 30%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid (470 mg, 1.04 mmol) in tetrahydrofurane (10 ml) was added carbonyldiimidazole (250 mg, 1.56 mmol) at room temperature. The solution was stirred at room temperature for 2 hours. To the mixture was added dimethylamine (2.0N in THF, 1.0 ml, 2.0 mmol). The resulted mixture was stirred at room temperature for 3 hours. Water (20 ml) was added to the reaction mixture. The solvent was removed in vacuo. The resulted mixture was dissolved in ethyl acetate (30 ml) and extracted with water (20 ml). The organic layer was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml), brine (20 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The resulted oil was stirred with ether overnight. The suspension was filtered to give a yellowish solid. The solid was purified by HPLC (CH3CN: Water=45:55) to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-N,N-dimethyl-propionamide as a white solid (160 mg, 30%): mp 80–82° C.; 1H NMR: δ(CDCl3): δ 0.33–0.39 (m, 2H), 0.60–0.68 (m, 2H), 1.21–1.30 (m, 1H), 2.25 (s, 3H), 2.90 (s, 3H), 2.97 (dd, J=5 Hz, the other doublet is buried, 1H), 3.05 (s, 3H), 3.87 (d, J=7.5 Hz, 2H), 3.94 (dd, J=10 Hz, the other doublet is buried, 1H), 5.83 (dd, J=5, 10 Hz, 1H), 6.69 (t, JH-F=75 Hz, 1H), 7.12–7.15 (m, 3H), 7.45 (d, J=7.5 Hz, 1H), 7.62 (t, J=7.5 Hz, 1H), 8.73 (d, J=8.5 Hz, 1H), 9.53 (s, 1H). 13C NMR (CDCl3): δ 3.8, 3.9, 10.8, 25.6, 35.4, 36.1, 37.7, 51.9, 74.5, 112.6, 116.7, 120.8, 114.9, 116.0, 118.5, 120.9, 123.4, 125.3, 131.9, 136.4, 138.0, 138.6, 140.7, 151.2, 168.7, 169.8, 169.9, 170.6; Anal. Calcd. for C26H27F2N3O6: C, 60.58; H, 5.28; N, 8.15. Found: C, 60.23; H, 5.26; N, 8.02.

후처리

  1. stirringThe resulted mixture was stirred at room temperature for 3 hours
  2. customThe solvent was removed in vacuo
  3. dissolutionThe resulted mixture was dissolved in ethyl acetate (30 ml)
  4. extractionextracted with water (20 ml)
  5. washThe organic layer was washed with saturated sodium bicarbonate solution (3×20 ml), water (20 ml), brine (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. stirringThe resulted oil was stirred with ether overnight
  9. filtrationThe suspension was filtered
  10. customto give a yellowish solid
  11. customThe solid was purified by HPLC (CH3CN: Water=45:55)

출처 및 근거

ORD 기록
ord-35b90b4d6a054177a3d490964a7c9c7c
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173058B2

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