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

HRID 1824270

反応式

HRID 1824270 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.[CH:32](=O)[CH3:33].[BH3-]C#N.[Na+]>CO.CC(O)=O.CCOC(C)=O>[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][CH2:32][CH3:33])=[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 177Acetaldehyde3 回HCID 5003444Sodium cyanoborohydride3 回HCID 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 58583310(1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-N2-ethyl-2,3-dihydro-1H-indene-1,2-diamine収率 101.1%

試薬・触媒・溶媒 3

HCID 176Acetic Acid触媒3 回HCID 887Methanol溶媒HCID 8857Ethyl Acetate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 (0.15 g, 0.33 mmol) in MeOH (3.3 mL) was sequentially added acetaldehyde (22 mg, 0.5 mmol) and AcOH (5 drops). This mixture was stirred for 30 min before addition of NaBH3CN (1 M solution in THF, 0.6 mL, 0.6 mmol). Stir at rt overnight. Add additional acetic acid (2 drops), acetaldehyde (29 μL, 0.5 mmol) and NaBH3CN (1 M solution in THF, 0.6 mL, 0.6 mmol). After 2 hr, add additional acetic acid (2 drops), acetaldehyde (29 μL, 0.5 mmol) and NaBH3CN (1 M solution in THF, 0.6 mL, 0.6 mmol). After 3 hr, dilute mixture with EtOAc and wash with sat. aq. NaHCO3 and extract with EtOAc (3×40 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated. Purify by biotage MPLC (90 g column, 100% ethyl acetate) to afford 0.16 g (44%) of (1R,2R)-N1-[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]-N2-ethyl-2,3-dihydro-1H-indene-1,2-diamine as a solid: 1H NMR (CDCl3) δ 0.84–1.05, 1.62–1.75, 2.78–2.86, 3.31–3.37, 3.52, 5.22, 5.52, 7.28–7.51; MS (ESI+) for C27H28Cl2N4 m/z 479 (M+H)+.

後処理

  1. waitAfter 2 hr
  2. waitAfter 3 hr
  3. washwash with sat. aq. NaHCO3
  4. extractionextract with EtOAc (3×40 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurify by biotage MPLC (90 g column, 100% ethyl acetate)

出典と根拠

ORDレコード
ord-4f088d0b85ad4572b58a6506a1486dbb
出典データセット
uspto-grants-2006_05
特許番号
US07041672B2

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