Triethylamine → n-((1r)-1-{5-[5-Chloro-3-fluoro-2-(2-methyl-2h-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-4,4-difluorocyclohex-1-ene-1-carboxamide

HRID 1160624Notes

Reaction equation

HRID 1160624 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][C:5]([C:8]([OH:10])=O)=[CH:4][CH2:3]1.[Cl:12][C:13]1[CH:14]=[C:15]([F:35])[C:16]([C:29]2[N:30]=[N:31][N:32]([CH3:34])[N:33]=2)=[C:17]([C:19]2[CH:20]=[C:21]([F:28])[C:22]([C@H:25]([NH2:27])[CH3:26])=[N:23][CH:24]=2)[CH:18]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C=O)C.CCOC(C)=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([F:35])[C:16]([C:29]2[N:30]=[N:31][N:32]([CH3:34])[N:33]=2)=[C:17]([C:19]2[CH:20]=[C:21]([F:28])[C:22]([C@H:25]([NH:27][C:8]([C:5]3[CH2:6][CH2:7][C:2]([F:1])([F:11])[CH2:3][CH:4]=3)=[O:10])[CH3:26])=[N:23][CH:24]=2)[CH:18]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 68714852((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)amineHCID 687178884,4-Difluorocyclohex-1-ene-1-carboxylic acid

Product 1

HCID 68717372n-((1r)-1-{5-[5-Chloro-3-fluoro-2-(2-methyl-2h-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-4,4-difluorocyclohex-1-ene-1-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The above carboxylic acid (223 mg, 1.37 mmol) and the compound of Reference Example 4 (482 mg, 1.37 mmol) were dissolved in 2.3 mL of degassed DMF. HOBT (21 mg, 0.14 mmol) and EDCI (303 mg, 1.58 mmol) were added, and the mixture was made basic with triethylamine (139 mg. 1.37 mmol). After 20 hours at ambient temperature, 10 mL of water and 1 mL of 10% sodium bicarbonate were added and the mixture was extracted with EtOAc. The combined organic layers were washed with water and brine, and then dried over sodium sulfate. Filtration and removal of solvent provided the crude product which was subjected to chromatography on silica gel eluting with 5 to 50% EtOAc in hexanes to give N-((1R)-1-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-4,4-difluorocyclohex-1-ene-1-carboxamide

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationFiltration and removal of solvent
  5. customprovided the crude product which

Sources & evidence

ORD record
ord-c57b1f0cd5c84b1b91b6cd2a8c35c5ac
Source dataset
uspto-grants-2010_10
Patent number
US07816380B2

Reaction notes

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