Acetic Acid → 8-{[3-(5,7-difluoro-1H-indol-3-yl)propyl]amino}-2,3,8,9-tetrahydropyrano[3,2-e]isoindol-1(7H)-one

HRID 1727392Notes

Reaction equation

HRID 1727392 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:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([F:26])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:27][CH2:28][CH:29]=O.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([F:26])[CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:27][CH2:28][CH2:29][NH: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

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 251409503-(5,7-difluoro-1H-indol-3-yl)propanalHCID 575676698-amino-2,3,8,9-tetrahydropyrano[3,2-e]isoindol-1(7H)-one

Product 1

HCID 690721438-{[3-(5,7-difluoro-1H-indol-3-yl)propyl]amino}-2,3,8,9-tetrahydropyrano[3,2-e]isoindol-1(7H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of (1) (202 mg, 0.99 mmol), 3-(5,7-difluoro-1H-indol-3-yl)propanal ((41), 247 mg, 1.09 mmol) in acetic acid (145 μl, 2.36 mmol) and methanol (10 ml) was added NaBH3CN (126 mg, 2.00 mmol) in portions. Resulting mixture was stirred for 2.0 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 70% EtOAc/Hexane to give (18), which was treated with 1 equivalent of etherate HCl to form HCl salt. MS (ES) m/z 412.2.

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 70% EtOAc/Hexane

Sources & evidence

ORD record
ord-44a7e0fcc94242ce90eff6920f2c1d5e
Source dataset
uspto-grants-2009_02
Patent number
US07495111B2

Reaction notes

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