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

HRID 1453350Notes

Reaction equation

HRID 1453350 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.N1(C2N=CC=CN=2)CCNCC1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[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

7

Reactant 4

HCID 8471TriethylamineHCID 887471-(2-Pyrimidinyl)piperazineHCID 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 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (200 mg, 0.48 mmol), 2-(piperazin-1-yl)pyrimidine (95 mg, 0.58 mmol) and triethylamine (0.20 mL, 1.45 mmol) in DMF (3 mL) was added HATU (220 mg, 0.58 mmol). The reaction mixture was stirred at rt for 2 h, diluted with H2O (˜6 mL) and the solids were collected by filtration, washed with H2O, dissolved into MeOH//THF (1:1, 4 mL) and treated with 1M aqueous NaOH (0.60 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 20 min in a sealed tube, additional 1 M aqueous NaOH (0.10 mL.) was added and the reaction was reheated at 80° C. for 10 min. The clear solution was diluted with H2O (1 mL), neutralized with 1M aqueous HCl (0.70 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O and dried under vacuum to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-(2-pyrimidinyl)-1-piperazinyl]carbonyl] (125 mg, 0.23 mmol, 48%) as a light yellow solid. LCMS: m/e 548 (M+H)+, ret time 1.52 min, column A, 2 minute gradient.

Workup

  1. filtrationthe solids were collected by filtration
  2. washwashed with H2O
  3. dissolutiondissolved into MeOH//THF (1:1, 4 mL)
  4. additiontreated with 1M aqueous NaOH (0.60 mL)
  5. stirringThe reaction mixture was stirred
  6. temperatureheated at 80° C. with microwave irradiation for 20 min in a sealed tube
  7. additionadditional 1 M aqueous NaOH (0.10 mL.) was added
  8. waitthe reaction was reheated at 80° C. for 10 min
  9. additionThe clear solution was diluted with H2O (1 mL)
  10. concentrationconcentrated
  11. customto remove organic solvents
  12. filtrationThe resultant solids were collected by filtration
  13. washwashed with H2O
  14. customdried under vacuum

Sources & evidence

ORD record
ord-5b13525edaf741e69b0300e942ed4726
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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