Acetic Acid → HCID 21955940, compound

HRID 2212984Notes

Reaction equation

HRID 2212984 reaction equation
O=[C:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=2)[NH:10][CH:9]=1.[CH3:19][NH:20][CH3:21].C([BH3-])#N.[Na+].C(O)(=O)C>C(O)C>[CH3:19][N:20]([CH3:21])[CH:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=2)[NH:10][CH:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 21955926HCID 21955926, compound

Product 1

HCID 21955940HCID 21955940, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-(2-oxo-cyclopentylmethyl)-1H-indole-5-carbonitrile (45 mg, 0.19 mMol), dimethylamine (1.92 mL, 3.78 mMol, 2.0 M/THF), sodium cyanoborohydride (0.12 g, 1.9 mMol) and acetic acid (0.2 mL) in ethanol (10 mL) was stirred for 16 h. The solution was cooled in an ice-bath and quenched with aqueous hydrochloric acid (2 mL, 1 N). The mixture was stirred for 5 min and then poured into a saturated aqueous solution of sodium bicarbonate (15 mL) and brine (10 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude material was purified by silica gel column chromatography using a step gradient of 0.5% MeOH/CHCl3-30% MeOH/CHCl3 to give 3-(2-dimethylamino-cyclopentylmethyl)-1H-indole-5-carbonitrile (13.0 mg, 26%) as a mixture of diastereomers. 1H NMR (400 MHz, DMSO-d6) δ 7.98 (1H, s), 7.50 (1H, d, J=8.4 Hz), 7.38 (2H, m), 2.89 (1H, m), 2.33 (9H, m), 1.82 (2H, m), 1.57 (2H, m), 1.42 (2H, m); LCMS (Method A: 4.6×50 mm XTERRA C-18 S5 column, 5 mL/min, 0–100% MeOH/H2O/0.1% TFA, 2 min gradient): Tr=1.09 min, m/e 268 (M+H)+.

Workup

  1. temperatureThe solution was cooled in an ice-bath
  2. customquenched with aqueous hydrochloric acid (2 mL, 1 N)
  3. additionpoured into a saturated aqueous solution of sodium bicarbonate (15 mL) and brine (10 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-80c15650ec6d403cb1df90c6ae6c8eef
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

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