Hydrochloric Acid → HCID 59828919, compound

HRID 1191126Notes

Reaction equation

HRID 1191126 reaction equation
Cl.C(OC([N:9]([CH2:16][C:17]1[CH:42]=[CH:41][C:20]([CH2:21][NH:22][C:23]2[C:33]3[CH2:32][CH2:31][N:30](C(=O)C(F)(F)F)[CH2:29][CH2:28][C:27]=3[CH:26]=[CH:25][C:24]=2[Cl:40])=[CH:19][CH:18]=1)[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=O)(C)(C)C.O.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O>[Cl:40][C:24]1[CH:25]=[CH:26][C:27]2[CH2:28][CH2:29][NH:30][CH2:31][CH2:32][C:33]=2[C:23]=1[NH:22][CH2:21][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][NH:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 11430Potassium CarbonateHCID 86624170HCID 86624170, compound

Product 1

HCID 59828919HCID 59828919, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Bubble hydrogen chloride into a solution of 6-{-4-[N-(tert-butoxycarbonyl)-N-(cyclohexyl)-aminomethyl]-benzylamino}-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (355 mg, 0.6 mmol) in EtOAc (5 mL) at room temperature. Stir the mixture for 1 h, and concentrate in vacuo. Dissolve the residue in methanol (5 mL) and add water (2 mL) and K2CO3 (1 g, 7.2 mmol). Stir the mixture at room temperature overnight. Concentrate the mixture in vacuo and partition the residue between water (20 mL) and DCM (20 mL). Extract the aqueous phase with DCM (2×20 mL). Dry the combined organic extracts over Na2SO4, filter, and concentrate in vacuo. Purify by reverse phase chromatography [Phenomonex C18(2) column (5×25 cm) eluting with a gradient of water:acetonitrile (0.1% TFA in each) 9:1 through 2:3 over 50 min, 118 mL/min]. Concentrate pure fractions and apply to a SCX column (3.5 g) eluting with methanol and 3N ammonia in methanol to obtain 7-chloro-6-{4-[N-(cyclohexyl)-aminomethyl]-benzylamino}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (204 mg, 86%).

Workup

  1. concentrationconcentrate in vacuo
  2. dissolutionDissolve the residue in methanol (5 mL)
  3. stirringStir the mixture at room temperature overnight
  4. concentrationConcentrate the mixture in vacuo
  5. custompartition the residue between water (20 mL) and DCM (20 mL)
  6. extractionExtract the aqueous phase with DCM (2×20 mL)
  7. dry with materialDry the combined organic extracts over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customPurify by reverse phase chromatography [Phenomonex C18(2) column (5×25 cm)
  11. washeluting with a gradient of water
  12. waitacetonitrile (0.1% TFA in each) 9:1 through 2:3 over 50 min
  13. concentrationConcentrate pure fractions
  14. washapply to a SCX column (3.5 g) eluting with methanol and 3N ammonia in methanol

Sources & evidence

ORD record
ord-0494a607a29d48049f6448f6ea3c2eff
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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