Triethylamine → 1-(2,2-Diethoxyethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxamide

HRID 592823Notes

Reaction equation

HRID 592823 reaction equation
[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=[C:7]1[C:15](O)=[O:16])[CH3:2].F[P-](F)(F)(F)(F)F.[N:28]1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(CC)CC.[OH-].[NH4+]>CN(C)C=O.CN(C1C=CN=CC=1)C.O>[CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=[C:7]1[C:15]([NH2:28])=[O:16])[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866837531-(2,2-Diethoxyethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylic Acid

Product 1

HCID 866837541-(2,2-Diethoxyethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxamideYield 96.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 195c (2.8 g, 10.0 mmol) in N,N-dimethylformamide (30 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (5.7 g, 15.0 mmol), Et3N (1.5 g, 15.0 mmol), and DMAP (128 mg, 1.0 mmol). The reaction mixture was stirred at room temperature for overnight. Saturated ammonium hydroxide (30 mL) was added and the resulting mixture was further stirred for 2 h. It was then diluted with water (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic phase was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (6:1 to 3:1) to afford 195d (2.7 g, 96%). MS-ESI: [M-EtOH+H]+ 235. 1H NMR (500 MHz, DMSO) δ 7.35 (bs, 1H), 6.70 (bs, 1H), 6.60 (s, 1H), 4.60 (t, J=5.5 Hz, 1H), 4.18 (d, J=4.0 Hz, 2H), 3.57-3.56 (m, 2H), 3.25 (m, 2H), 2.57 (t, J=6.0 Hz, 2H), 2.40 (t, J=6.0 Hz, 2H), 1.71 (t, J=5.0 Hz, 2H), 1.64 (t, J=5.0 Hz, 2H), 1.01 (t, J=7.0 Hz, 6H).

Workup

  1. stirringthe resulting mixture was further stirred for 2 h
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. concentrationThe combined organic phase was concentrated under reduced pressure
  4. customthe residue was purified by silica-gel column chromatography
  5. washeluting with petroleum ether/ethyl acetate (6:1 to 3:1)

Sources & evidence

ORD record
ord-f843f66f53da410387bf46a07bab1461
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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