Ammonia → tert-butyl 7-carbamoyl-1H-indole-4-carboxylate

HRID 906116Notes

Reaction equation

HRID 906116 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:14]([C:17]([OH:19])=O)=[C:13]2[C:9]=1[CH:10]=[CH:11][NH:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:21](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.N.CO>CN(C)C=O.C(OCC)(=O)C>[C:17]([C:14]1[C:13]2[NH:12][CH:11]=[CH:10][C:9]=2[C:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:16][CH:15]=1)(=[O:19])[NH2:21]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 887MethanolHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674031504-(tert-butoxycarbonyl)-1H-indole-7-carboxylic acid

Product 1

HCID 67404011tert-butyl 7-carbamoyl-1H-indole-4-carboxylateYield 50.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-(tert-butoxycarbonyl)-1H-indole-7-carboxylic acid (0.36 g, 1.38 mmol), HATU (0.30 g, 1.60 mmol), 4-methylmorpholine (0.75 mL, 6.89 mmol) and a 2M solution of ammonia in methanol (1.80 mL, 3.45 mmol) in dimethylformamide (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate (150 mL) and the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by column chromatography chloroform: (10% ammonium hydroxide in methanol) 9:1 as eluent afforded tert-butyl 7-carbamoyl-1H-indole-4-carboxylate (0.18 g, 50%). 1H NMR (400 MHz, CDCl3): 10.50 (bs, 1H), 7.83 (d, 1H), 7.43 (m, 2H), 7.15 (m, 1H), 6.30 (bd, 2H), 1.62 (s, 9H). MS (EI) for C14H16N2O3: 259 (M−H).

Workup

  1. washthe organic layer was washed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatography chloroform

Sources & evidence

ORD record
ord-9c89c34572794eb686823a77859ac0a7
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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