Cyanogen Bromide → HCID 59432307, compound

HRID 507057Notes

Reaction equation

HRID 507057 reaction equation
[N:1]#[C:2]Br.[C:4]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=2)[C:13]2[CH:34]=[C:35]([CH2:42][CH3:43])[C:36]([C:38]([F:41])([F:40])[F:39])=[CH:37][C:12]1=2)=[O:10])([CH3:7])([CH3:6])[CH3:5].C(N(C(C)C)CC)(C)C>O1CCCC1>[C:4]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:14]([N:18]([CH2:19][C:20]2[CH:21]=[C:22]([C:30]([F:31])([F:33])[F:32])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=2)[C:2]#[N:1])[C:13]2[CH:34]=[C:35]([CH2:42][CH3:43])[C:36]([C:38]([F:41])([F:39])[F:40])=[CH:37][C:12]1=2)=[O:10])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 81531DiisopropylethylamineHCID 59432389HCID 59432389, compound

Product 1

HCID 59432307HCID 59432307, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
67.5 °C

Procedure

Add cyanogen bromide (0.352 g, 3.33 mmol) to a solution of (S)-5-(3,5-Bis-trifluoromethyl-benzylamino)-7-ethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (0.647 g, 1.11 mmol) and diisopropylethylamine (0.679 mL, 3.89 mmol) in tetrahydrofuran (3 mL) at room temperature under nitrogen and heat the mixture at 65-70° C. for 16 hours and then for another 90° C. 16 h. Partition the cooled mixture between dichloromethane (40 mL) and brine (40 mL), separated layers. Extract aqueous with more dichloromethane (40 mL). Combine organic layers, dry over anhydrous sodium sulfate, filter and concentrated under reduced pressure. Purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0-20%), to provide the title compound (0.517 g, 76%), MS (ES+): 627 (M+NH4), 632 (M+Na).

Workup

  1. customfor another 90° C
  2. custom16 h
  3. customPartition the cooled mixture between dichloromethane (40 mL) and brine (40 mL)
  4. customseparated layers
  5. dry with materialCombine organic layers, dry over anhydrous sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrated under reduced pressure
  8. customPurify the residue by column chromatography on silica gel
  9. washeluting with ethyl acetate/hexanes (0-20%)

Sources & evidence

ORD record
ord-5fc09bed1b86481f9597a3bc1ab3d14a
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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