Water → 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoro-1-(2-hydroxyethyl)-1H-indol-5-yl)cyclopropanecarboxamide

HRID 1908569Notes

Reaction equation

HRID 1908569 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][C:24]=4[F:25])[NH:21][CH:20]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[CH:30]([CH:32]=O)=[O:31].O.[BH3-]C#N.[Na+]>CO.CC#N.O.C(O)(=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][C:24]=4[F:25])[N:21]([CH2:32][CH2:30][OH:31])[C:20]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

8

Reactant 4

HCID 962WaterHCID 7860GlyoxalHCID 5003444Sodium cyanoborohydrideHCID 59129318HCID 59129318, compound

Product 1

HCID 591291721-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoro-1-(2-hydroxyethyl)-1H-indol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a solution of 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoroindolin-5-yl)cyclopropanecarboxamide (340 mg, 0.86 mmol) in anhydrous MeOH (5.7 mL) containing 1% of acetic acid was added glyoxal 40% in water (0.60 mL, 5.2 mmol) at room temperature under N2. After 20 min of stirring, NaBH3CN (120 mg, 1.9 mmol) was added in one portion and the reaction mixture was stirred overnight at room temperature. The solvent was removed under reduced pressure and the residue obtained was purified by column chromatography on silica gel (10-40% ethyl acetate/hexanes) providing a pale yellow oil which was treated with 50/50 CH3CN—H2O containing 0.05% TFA and CDCl3. Solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (20-35% ethyl acetate/hexanes) to give 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-6-fluoro-1-(2-hydroxyethyl)-1H-indol-5-yl)cyclopropanecarboxamide. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J=7.7 Hz, 1H), 7.30 (d, J=2.1 Hz, 1H), 6.93 (dd, J=1.6, 7.9 Hz, 1H), 6.90 (d, J=1.6 Hz, 1H), 6.90 (d, J=1.6 Hz, 1H), 6.78 (d, J=7.9 Hz, 1H), 6.08 (s, 1H), 5.92 (s, 2H), 4.21 (dd, J=6.9, 6.9 Hz, 2H), 3.68 (m, 2H), 2.28 (s, 1H), 1.60 (dd, J=3.7, 6.7 Hz, 2H), 1.35-1.32 (m, 9H), 1.04 (dd, J=3.7, 6.8 Hz, 2H). MS (ESI) m/e (M+H+) 439.0.

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. customThe solvent was removed under reduced pressure
  3. customthe residue obtained
  4. customwas purified by column chromatography on silica gel (10-40% ethyl acetate/hexanes)
  5. customproviding a pale yellow oil which
  6. customSolvent was removed under reduced pressure
  7. customthe residue was purified by column chromatography on silica gel (20-35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2721098f817344e6b4a16a24304f2b11
Source dataset
uspto-grants-2013_12
Patent number
US08598181B2

Reaction notes

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