1,2-Dichloroethane → HCID 58017551, compound

HRID 1642761Notes

Reaction equation

HRID 1642761 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([O:9][C:10](=[O:13])[CH2:11][CH3:12])[C:3]=1[C:14]([CH3:20])([CH3:19])[CH2:15][C:16]([OH:18])=[O:17].[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N:48]2[CH:52]=[N:51][N:50]=[N:49]2)=[C:26]([CH:47]=1)[CH2:27][NH:28][C:29]([C@H:31]1[N:35]([C:36](=[O:46])[C@@H:37]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)O)[N:34]=[CH:33][CH2:32]1)=[O:30].C(Cl)CCl>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([O:9][C:10](=[O:13])[CH2:11][CH3:12])[C:3]=1[C:14]([CH3:19])([CH3:20])[CH2:15][C:16]([O:18][C@H:37]([C:39]1[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=1)[C:36]([N:35]1[C@H:31]([C:29](=[O:30])[NH:28][CH2:27][C:26]2[CH:47]=[C:22]([Cl:21])[CH:23]=[CH:24][C:25]=2[N:48]2[CH:52]=[N:51][N:50]=[N:49]2)[CH2:32][CH:33]=[N:34]1)=[O:46])=[O:17]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 44537923(5S)-N-[5-Chloro-2-(1H-tetrazol-1-yl)benzyl]-1-[(2R)-2-(4-fluorophenyl)-2-hydroxyacetyl]-4,5-dihydro-1H-pyrazole-5-carboxamideHCID 57425266HCID 57425266, compound

Product 1

HCID 58017551HCID 58017551, compoundYield 92.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(2,4-dimethyl-6-(propionyloxy)phenyl)-3-methylbutanoic acid (160 mg, 0.57 mmol) and (S)—N-(5-chloro-2-(1H-tetrazol-1-yl)benzyl)-1-((R)-2-(4-fluorophenyl)-2-hydroxyacetyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (263 mg, 0.57 mmol) in DCM (3 mL) and DMF (3 mL) was added EDC (165 mg, 0.86 mmol) and DMAP (7 mg, 0.06 mmol). The clear colorless solution was stirred at rt for 48 h. The mixture was diluted with DCM and washed with water, 1M HCl and sat NaHCO3. The organic phase was dried, filtered, evaporated and purified by flash chromatography (DCM/EtOAc gradient from 4:1 to 2:1) to give (R)-2-((S)-5-(5-chloro-2-(1H-tetrazol-1-yl)benzylcarbamoyl)-4,5-dihydro-1H-pyrazol-1-yl)-1-(4-fluorophenyl)-2-oxoethyl 3-(2,4-dimethyl-6-(propionyloxy)phenyl)-3-methylbutanoate (380 mg, 92%) as a semisolid.

Workup

  1. washwashed with water, 1M HCl
  2. customThe organic phase was dried
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by flash chromatography (DCM/EtOAc gradient from 4:1 to 2:1)

Sources & evidence

ORD record
ord-94c7fe50ecda437e8ee5fb31e5e8aa2a
Source dataset
uspto-grants-2012_02
Patent number
US08119673B2

Reaction notes

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