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

反応式

HRID 1612357 の反応式
[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

参加物

7

反応物 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

生成物 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-diamine収率 98.1%

試薬・触媒・溶媒 3

HCID 176Acetic Acid触媒HCID 887Methanol溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-cc9a8b16974a4f97a061b12a2484e534
出典データセット
uspto-grants-2006_01
特許番号
US06992087B2

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