Hydrochloric Acid → HCID 67096903, compound

HRID 2078663Notes

Reaction equation

HRID 2078663 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:32][C@@H:33]([C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([Cl:47])[CH:42]=1)[O:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1)[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:25]=[C:24]3[C:20]([C:21]([C:29]([OH:31])=O)=[CH:22][N:23]3[CH:26]([CH3:28])[CH3:27])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:60][S:61]([NH2:64])(=[O:63])=[O:62].C1CCN2C(=NCCC2)CC1.Cl>CN(C)C=O>[Cl:47][C:43]1[CH:42]=[C:41]([C@@H:33]([O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH2:32][N:8]([CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:25]=[C:24]4[C:20]([C:21]([C:29]([NH:64][S:61]([CH3:60])(=[O:63])=[O:62])=[O:31])=[CH:22][N:23]4[CH:26]([CH3:28])[CH3:27])=[CH:19][CH:18]=3)=[CH:15][CH:16]=2)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:46]=[CH:45][CH:44]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 67097026HCID 67097026, compound

Product 1

HCID 67096903HCID 67096903, compoundYield 91.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-[4-[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-amino]ethyl]phenyl]-1-isopropyl-1H-indole-3-carboxylic acid (131 mg) in N,N-dimethylformamide (2 mL) was added 1,1′-carbonyldiimidazole (35 mg) at room temperature under nitrogen, and the mixture was stirred at the same temperature for 2.5 hours. To this one were added methanesulfonamide (46 mg) and 1,8-diazabicyclo[5.4.0]-7-undecene (72 mg) at room temperature, and the mixture was stirred at 60° C. for 10 hours. The resulting mixture was poured into 0.1N hydrochloric acid and the aqueous layer was extracted with ethyl acetate. The organic layer was washed successively with 0.1N hydrochloric acid three times and brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform/methanol=200/1 to 100/1) to give tert-butyl [(2R)-2-(3-chlorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)ethyl][2-[4-[1-isopropyl-3-[[(methylsulfonyl)amino]-carbonyl]-1H-indol-6-yl]phenyl]ethyl]carbamate (134 mg).

Workup

  1. stirringthe mixture was stirred at 60° C. for 10 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe organic layer was washed successively with 0.1N hydrochloric acid three times and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel (chloroform/methanol=200/1 to 100/1)

Sources & evidence

ORD record
ord-e55126261c8a42f585fce07726656309
Source dataset
uspto-grants-2011_04
Patent number
US07928264B2

Reaction notes

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