Methoxyacetaldehyde → (1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-N2-(2-methoxyethyl)-2,3-dihydro-1H-indene-1,2-diamine

HRID 1612357

반응식

HRID 1612357 반응식
[CH:1]1([C:4]2[C:5]([NH:21][C@@H:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][C@H:23]3[NH2:31])=[N:6][C:7]([CH:18]3[CH2:20][CH2:19]3)=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])[N:9]=2)[CH2:3][CH2:2]1.[CH3:32][O:33][CH2:34][CH:35]=O.[BH3-]C#N.[Na+]>CO.C(O)(=O)C.C([O-])(O)=O.[Na+]>[CH:1]1([C:4]2[C:5]([NH:21][C@@H:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][C@H:23]3[NH:31][CH2:35][CH2:34][O:33][CH3:32])=[N:6][C:7]([CH:18]3[CH2:19][CH2:20]3)=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])[N:9]=2)[CH2:2][CH2:3]1

참가 물질

7

반응물 3

HCID 91563MethoxyacetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 58583281(1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-2,3-dihydro-1H-indene-1,2-diamine

생성물 1

HCID 58583433(1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-N2-(2-methoxyethyl)-2,3-dihydro-1H-indene-1,2-diamine수율 98.1%

시약·촉매·용매 3

HCID 176Acetic Acid촉매HCID 887Methanol용매HCID 516892Sodium Bicarbonate용매

실험 절차

To a solution of (1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-2,3-dihydro-1H-indene-1,2-diamine (0.10 g, 0.22 mmol) in MeOH (2 mL) containing acetic acid (2 drops) and methoxyacetaldehye (49 mg, 0.66 mmol) was added NaBH3CN (1 M solution in THF, 0.8 mL, 0.8 mmol). The mixture was stirred at rt overnight. Dilute with sat. aq. NaHCO3 and extract ED with EtOAc (3×30 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated to afford an oil that was purified by biotage MPLC (90 g column, 10% ethyl acetate/hexanes) to afford 0.11 g (20%) of (1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-N2-(2-methoxyethyl)-2,3-dihydro-1H-indene-1,2-diamine as a solid: 1H NMR (CDCl3) δ 0.60-1.01, 1.45-1.70, 2.83-2.99, 3.22-3.33, 3.47-3.56, 5.19, 5.53, 7.11-7.42; MS (ESI+) for C28H30Cl2N4O m/z 509 (M+H)+.

후처리

  1. extractionextract
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford an oil that
  6. customwas purified by biotage MPLC (90 g column, 10% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-cc9a8b16974a4f97a061b12a2484e534
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06992087B2

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