Water → HCID 178484210, compound

HRID 1922420Notes

Reaction equation

HRID 1922420 reaction equation
C1(O[C:8](=O)[N:9](C)[CH2:10][CH2:11][N:12]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]3[CH:19]=[C:20]([NH:23][C:24]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)=[NH:25])[CH:21]=[CH:22][C:13]2=3)C=CC=CC=1.[OH-].[Na+].O>C(O)C.CO.C(Cl)Cl>[CH3:8][NH:9][CH2:10][CH2:11][N:12]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]2[CH:19]=[C:20]([NH:23][C:24]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[NH:25])[CH:21]=[CH:22][C:13]1=2

Participants

6

Reactant 3

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 178484211HCID 178484211, compound

Product 1

HCID 178484210HCID 178484210, compoundYield 40.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of phenyl-methyl(2-(7-(thiophene-2-carboximidamido)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)ethyl)carbamate (200 mg, 0.45 mmol) in 12 mL ethanol was treated with NaOH (178 mg, 4.46 mmol) followed by H2O (5 mL). The mixture was then heated at reflux for 6 hours. A TLC analysis indicated that starting material is present. At this moment, NaOH (90 mg) was added and heating was continued for 1 hour. The solution was concentrated to about 5 mL and partitioned between CH2Cl2 (100 mL) and brine (20 mL). After extraction, the organic layer was separated and the aqueous layer was extracted once more with CH2Cl2 (50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to give a yellow oil. This residue was subjected to flash chromatography on silica gel using 2.5-10% 2M NH3 in MeOH/CH2Cl2 to give a yellow solid (60 mg, 40.5%). 1H-NMR (DMSO-d6) δ 7.70 (d, J=3.3 Hz, 1H), 7.57 (d, J=4.8 Hz, 1H), 7.09-7.06 (m, 1H), 6.91-6.88 (m, 1H), 6.64-6.62 (m, 2H), 6.33-6.31 (m, 2H), 3.14 (t, J=6.3 Hz, 2H), 2.85-2.70 (m, 2H), 2.77-2.61 (m, 4H), 2.31 (s, 3H), 1.67-1.62 (m, 2H), 1.50-1.46 (m, 2H). MS (EI): 329.2 (M+1). ESI-HRMS calculated for C18H25N4S (MH+): 329.1794, Observed: 329.1802.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 6 hours
  3. temperatureheating
  4. concentrationThe solution was concentrated to about 5 mL
  5. custompartitioned between CH2Cl2 (100 mL) and brine (20 mL)
  6. extractionAfter extraction
  7. customthe organic layer was separated
  8. extractionthe aqueous layer was extracted once more with CH2Cl2 (50 mL)
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a yellow oil

Sources & evidence

ORD record
ord-0becff4953ae4ec1998ede4a363dec1e
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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