Diisopropylethylamine → 2-(2,2,2-Trifluoro-1,1-dimethyl-ethyl)-5,6,7,8-tetrahydro-quinoline-6-carboxylic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-amide

HRID 1697477Notes

Reaction equation

HRID 1697477 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH2:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:14][C:15]([F:33])([F:32])[C:16]([C:19]1[CH:28]=[CH:27][C:26]2[CH2:25][C@H:24]([C:29](O)=[O:30])[CH2:23][CH2:22][C:21]=2[N:20]=1)([CH3:18])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN1C(=O)CCC1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH:13][C:29]([CH:24]3[CH2:23][CH2:22][C:21]4[N:20]=[C:19]([C:16]([CH3:18])([CH3:17])[C:15]([F:33])([F:32])[F:14])[CH:28]=[CH:27][C:26]=4[CH2:25]3)=[O:30])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2585641-Acetyl-6-aminoindolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58118632(R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid

Product 1

HCID 581254942-(2,2,2-Trifluoro-1,1-dimethyl-ethyl)-5,6,7,8-tetrahydro-quinoline-6-carboxylic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-amideYield 64.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 1-acetyl-6-amino-indoline (32 mg, 0.18 mmol), (R)-2-(1,1,1-trifluoro-2-methylpropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (40 mg, 0.14 mmol) was added HATU (79 mg, 0.21 mmol) in NMP (0.7 mL), followed by N,N-diisopropylethylamine (73 μL, 0.42 mmol). After 1.3 h, the reaction was heated to 60° C. After 25 h, the material was filtered and purified by reverse-phase HPLC (40-75% ACN in 0.1% HCO2H/H2O). The fractions were stirred with MP-carbonate resin (1.0 g, 3.0 mmol/g) overnight, filtered and concentrated to afford the amide (40 mg, 64%) as a solid foam. 1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.21 (d, J=1.8 Hz, 1H), 7.57 (d, J=8.1 Hz, 1H), 7.51 (d, J=8.1 Hz, 1H), 7.38 (dd, J=1.8, 8.1 Hz, 1H), 7.13 (d, J=8.1 Hz, 1H), 4.09 (t, J=8.5 Hz, 2H), 3.08 (t, J=8.5 Hz, 2H), 3.02-2.85 (m, 4H), 2.85-2.74 (m, 1H), 2.18-2.12 (m, 1H), 2.16 (s, 3H), 1.93-1.82 (m, 1H), 1.55 (s, 6H); m/z=446.5 (M+1)+.

Workup

  1. waitAfter 25 h
  2. filtrationthe material was filtered
  3. custompurified by reverse-phase HPLC (40-75% ACN in 0.1% HCO2H/H2O)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4f29b0d86bdc489cb1f68d952a370964
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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