Acetic Acid → 3-{3-[(1-oxo-1,2,3,7,8,9-hexahydropyrano[3,2-e]isoindol-8-yl)amino]propyl}-1H-indole-5-carbonitrile

HRID 1727389Notes

Reaction equation

HRID 1727389 reaction equation
[NH2:1][CH:2]1[CH2:14][O:13][C:12]2[CH:11]=[CH:10][C:9]3[CH2:8][NH:7][C:6](=[O:15])[C:5]=3[C:4]=2[CH2:3]1.F[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH2:27][CH2:28]C=O.C(O)(=O)C.[BH3-][C:36]#[N:37].[Na+]>CO>[O:15]=[C:6]1[C:5]2[C:4]3[CH2:3][CH:2]([NH:1][CH2:28][CH2:27][CH2:26][C:20]4[C:19]5[C:23](=[CH:24][CH:25]=[C:17]([C:36]#[N:37])[CH:18]=5)[NH:22][CH:21]=4)[CH2:14][O:13][C:12]=3[CH:11]=[CH:10][C:9]=2[CH2:8][NH:7]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 118460104-(5-fluoro-1H-indol-3-yl)butanalHCID 575676698-amino-2,3,8,9-tetrahydropyrano[3,2-e]isoindol-1(7H)-one

Product 1

HCID 462252643-{3-[(1-oxo-1,2,3,7,8,9-hexahydropyrano[3,2-e]isoindol-8-yl)amino]propyl}-1H-indole-5-carbonitrileYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of (1) (60 mg, 0.294 mmol), 4-(5-fluoro-1H-indol-3-yl)butanal (21), 64 mg, 0.309 mmol) in acetic acid (37 μl, 0.62 mmol) and methanol (2 ml) was added NaBH3CN (37 mg, 0.59 mmol) in portions. Resulting mixture was stirred for 1.5 hr. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 and washed with 1 N NaOH and saturated NaCl. The organic solution was dried over Na2SO4 and concentrated in vacuo. The compound was purified on silica gel eluting with 60% EtOAc/Hexane to give (20) as a solid (78 mg, 69%). The title compound was dissolved in methylene chloride and treated with 1 equivalent of etherate HCl to give HCl salt. MS (ES) m/z 385.2.

Workup

  1. customResulting mixture
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2
  4. washwashed with 1 N NaOH and saturated NaCl
  5. dry with materialThe organic solution was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe compound was purified on silica gel eluting with 60% EtOAc/Hexane

Sources & evidence

ORD record
ord-a0a84ece401f42cc9667b85116cd35f1
Source dataset
uspto-grants-2009_02
Patent number
US07495111B2

Reaction notes

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