Hydrochloric Acid → 3-Chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (4'-methanesulfonylmethyl-4-methoxy-biphenyl-3-ylmethyl)-(4-methylamino-cyclohexyl)-amide hydrochloride

HRID 2389665Notes

Reaction equation

HRID 2389665 reaction equation
[Cl:1][C:2]1[C:3]2[C:48]([F:49])=[CH:47][CH:46]=[C:45]([F:50])[C:4]=2[S:5][C:6]=1[C:7]([N:9]([CH2:25][C:26]1[CH:27]=[C:28]([C:34]2[CH:39]=[CH:38][C:37]([CH2:40][S:41]([CH3:44])(=[O:43])=[O:42])=[CH:36][CH:35]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33])[CH:10]1[CH2:15][CH2:14][CH:13]([N:16](C)[C:17](=O)OC(C)(C)C)[CH2:12][CH2:11]1)=[O:8].Cl.CC(OC)(C)C>C(Cl)Cl>[ClH:1].[CH3:44][S:41]([CH2:40][C:37]1[CH:38]=[CH:39][C:34]([C:28]2[CH:29]=[CH:30][C:31]([O:32][CH3:33])=[C:26]([CH2:25][N:9]([CH:10]3[CH2:11][CH2:12][CH:13]([NH:16][CH3:17])[CH2:14][CH2:15]3)[C:7]([C:6]3[S:5][C:4]4[C:45]([F:50])=[CH:46][CH:47]=[C:48]([F:49])[C:3]=4[C:2]=3[Cl:1])=[O:8])[CH:27]=2)=[CH:35][CH:36]=1)(=[O:42])=[O:43]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 15413tert-Butyl methyl etherHCID 59683596tert-Butyl {4-[(3-chloro-4,7-difluoro-benzo[b]thiophene-2-carbonyl)-(4'-methanesulfonylmethyl-4-methoxy-biphenyl-3-ylmethyl)-amino]-cyclohexyl}-methyl-carbamate

Product 1

HCID 683144633-Chloro-4,7-difluoro-benzo[b]thiophene-2-carboxylic acid (4'-methanesulfonylmethyl-4-methoxy-biphenyl-3-ylmethyl)-(4-methylamino-cyclohexyl)-amide hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl carbamate 199 (224 mg, 0.30 mmol) is deprotected using Method F. On removal of the solvents in vacuo, the residue is suspended in aqueous NaHCO3 (20 mL) and extracted into DCM (3×20 mL). The combined DCM phases are washed with water (2×20 μL) and brine (20 mL) then dried (Na2SO4) and reduced in vacuo. The free base thus obtained is converted to the HCl salt by Method H. The isolated salt is then dissolved in the minimum amount of DCM and added dropwise to cold (0° C.) TBME (25 mL). The resultant pale yellow precipitate is isolated by filtration, washed with TBME (10 mL) and diethyl ether (10 mL) and dried to afford the title compound.

Workup

  1. customOn removal of the solvents in vacuo
  2. extractionextracted into DCM (3×20 mL)
  3. washThe combined DCM phases are washed with water (2×20 μL) and brine (20 mL)
  4. dry with materialthen dried (Na2SO4)
  5. customThe free base thus obtained
  6. customThe resultant pale yellow precipitate is isolated by filtration
  7. washwashed with TBME (10 mL) and diethyl ether (10 mL)
  8. customdried

Sources & evidence

ORD record
ord-b5f0e02291454d1f9ad7379ba9ca20ef
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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