Hydrochloric Acid → HCID 59003127, compound

HRID 2353923Notes

Reaction equation

HRID 2353923 reaction equation
[C:1]([O:4]C(=O)C)(=[O:3])[CH3:2].[CH:8]([O:11][C:12]([N:14]1[CH2:20][CH2:19][CH2:18][CH:17]([NH:21][CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)[C:16]2[C:37]([F:42])=[C:38]([CH3:41])[CH:39]=[CH:40][C:15]1=2)=[O:13])([CH3:10])[CH3:9].N1C=CC=CC=1.Cl>ClCCl>[C:1]([O-:4])(=[O:3])[CH3:2].[C:1]([N:21]([CH2:22][C:23]1[CH:24]=[C:25]([C:33]([F:35])([F:36])[F:34])[CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=1)[CH:17]1[CH2:18][CH2:19][CH2:20][N:14]([C:12]([O:11][CH:8]([CH3:10])[CH3:9])=[O:13])[C:15]2[CH:40]=[CH:39][C:38]([CH3:41])=[C:37]([F:42])[C:16]1=2)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 86616076HCID 86616076, compound

Product 2

HCID 175AcetateHCID 59003127HCID 59003127, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Add 3,5-bis(trifluoromethyl)benzylamine (23 mg, 0.095 mmol) followed by titanium isopropoxide (0.035 mL, 0.12 mmol) to isopropyl 6-fluoro-7-methyl-5-oxo-2,3,4,5-tetrahydro benzo[b]azepine-1-carboxylate (24 mg, 0.086 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 2 days. Filter the residue over silica cartridge, eluting with hexanes/ethyl acetate (8:1) to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-7-methyl-2,3-dihydro-benzo[b]azepine-1-carboxylic (34 mg, 79%). Add methanol (1 mL) and platinum oxide (2 mg, 0.007 mmol) and hydrogenate the mixture at 1 atmosphere and room temperature for 7 h. Filter through celite and remove the solvent under reduced pressure to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-7-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (36 mg, quantitative). Add acetic anhydride (0.1 mL, 1.07 mmol) dropwise to a suspension of the amine (36 mg, 0.071 mmol) and pyridine (0.1 mL g, 1.07 mmol) in dichloromethane (0.5 mL) under nitrogen cooled to 0° C. After the addition is complete, remove the cooling bath and warm the reaction to room temperature and stir for 12 h. Add 1 N hydrochloric acid and extract with dichloromethane (3×10 mL). Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Chromatograph the residue over silica cartridge, eluting with hexanes/ethyl:acetate (6:1), to afford the title compound (18 mg, 46%); MS (ES+): 549 (M+H)

Workup

  1. additionAfter the addition
  2. customremove the cooling bath
  3. temperaturewarm
  4. customthe reaction to room temperature
  5. extractionextract with dichloromethane (3×10 mL)
  6. dry with materialDry the organic layer over anhydrous sodium sulfate
  7. filtrationfilter
  8. customremove the solvent under reduced pressure
  9. washChromatograph the residue over silica cartridge, eluting with hexanes/ethyl

Sources & evidence

ORD record
ord-bed0dd7ea1ca4137b8d952d5f20457ea
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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