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 1824272Notes

Reaction equation

HRID 1824272 reaction equation
[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

Participants

7

Reactant 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

Product 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-diamineYield 98.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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 5.09 (M+H)+.

Workup

  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)

Sources & evidence

ORD record
ord-4e3bddf800944d07a7aca4fc377f2353
Source dataset
uspto-grants-2006_05
Patent number
US07041672B2

Reaction notes

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