Hydrochloric Acid → 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 1453377Notes

Reaction equation

HRID 1453377 reaction equation
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+].Cl>CN(C=O)C.O.C1COCC1.CO.C(N(CC)CC)C>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68832135methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 666396797H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (366 mg, 0.88 mmol), 2-N,N-dimethyl-2-(methylamino)acetamide (120 mg, 1.03 mmol) and triethylamine (0.37 mL) in DMF (6 mL) was added HATU (400 mg, 1.05 mmol). The reaction mixture was stirred at rt for 2 h, diluted with H2O (˜20 mL) and the resulting solids were collected by filtration, washed with H2O and dried on the filter with aspirator vacuum for 1 h. The solids were dissolved into THF/MeOH (1:1, 6 mL) and 1M NaOH (aq.) (1.5 mL, 1.5 mmol). The reaction mixture was heated in a sealed tube with microwave irradiation at 85° C. for 20 min. The reaction was cooled, neutralized with 1M HCl (aq.) (1.5 mL, 1.5 mmol) and concentrated to remove organic solvents. The residue was slurried with H2O and the solids were collected by filtration, flushed with H2O and dried to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[[2-(dimethylamino)-2-oxoethyl]methylamino]carbonyl]- (406 mg, 0.81 mmol, 92%) as a yellow solid. Mixture of amide rotamers: 1HNMR (300 MHz, DMSO-d6) δ 12.58 (br s, 1H), 8.17 (br s, 0.5H), 8.13 (br s, 0.5H), 7.89 (d, J=8.8 Hz, 1H), 7.66-7.45 (m, 5H), 7.07 (br s, 0.5H), 6.90 (br s, 0.5H), 5.24-4.96 (m, 1H), 4.39-4.03 (m, 3H), 3.08-2.75 (m, 7H), 2.63 (s, 1.5H), 2.54 (s, 1.5H), 2.14-1.63 (m, 6H), 1.52-1.04 (m, 4H). LCMS: m/e 498 (M−H)−, ret time 1.36 min, column A, 2 minute gradient.

Workup

  1. filtrationthe resulting solids were collected by filtration
  2. washwashed with H2O
  3. customdried on the
  4. filtrationfilter with aspirator vacuum for 1 h
  5. temperatureThe reaction mixture was heated in a sealed tube with microwave irradiation at 85° C. for 20 min
  6. temperatureThe reaction was cooled
  7. concentrationconcentrated
  8. customto remove organic solvents
  9. filtrationthe solids were collected by filtration
  10. customflushed with H2O
  11. customdried

Sources & evidence

ORD record
ord-913f58f6b69c4399b5ca078fd5f9ff8c
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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