Hydrochloric Acid → HCID 86598958, compound

HRID 2220429Notes

Reaction equation

HRID 2220429 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:31][C@H:32]([OH:39])[C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23](O)=[O:24])=[C:19]([O:26][CH2:27][CH:28]([CH3:30])[CH3:29])[CH:18]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:52][S:53]([NH2:56])(=[O:55])=[O:54].N1CCCN2CCCCCC=12.Cl>CN(C)C=O.O>[OH:39][C@H:32]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)[CH2:31][N:8]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([NH:56][S:53]([CH3:52])(=[O:55])=[O:54])=[O:24])=[C:19]([O:26][CH2:27][CH:28]([CH3:29])[CH3:30])[CH:18]=2)=[CH:13][CH:12]=1)[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 69102782HCID 69102782, compound

Product 1

HCID 86598958HCID 86598958, compoundYield 32.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4′-[2-[[tert-butoxycarbonyl][(2R)-2-hydroxy-2-(3-pyridyl)ethyl]amino]ethyl]-3-isobutoxy-4-biphenylcarboxylic acid (170 mg) in N,N-dimethylformamide (1.70 ml) was added 1,1′-carbonylbis(1H-imidazole) (61.7 mg) and the mixture was stirred at room temperature for 1 hour under nitrogen atmosphere. To the reaction mixture were added methanesulfonamide (36.3 mg) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.057 ml) and the mixture was stirred at 120° C. for 12 hours. After cooling to room temperature, to the reaction mixture was added water (10 ml) and the pH was adjusted to 5.98 with 0.1N hydrochloric acid. The mixture was extracted with ethyl acetate (twice), washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation under reduced pressure gave a crude produce which was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1.5) and further purification by column chromatography on silica gel (eluent: chloroform/methanol=100/0 to 99/1) gave tert-butyl [(2R)-2-hydroxy-2-(3-pyridyl)ethyl][2-[3′-isobutoxy-4′-[[(methylsulfonyl)amino]carbonyl]-4-biphenylyl]ethyl]carbamate (63 mg) as a white foam.

Workup

  1. stirringthe mixture was stirred at 120° C. for 12 hours
  2. temperatureAfter cooling to room temperature, to the reaction mixture
  3. extractionThe mixture was extracted with ethyl acetate (twice),
  4. washwashed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration
  7. customfollowed by evaporation under reduced pressure
  8. customgave a crude
  9. customproduce which
  10. customwas purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/1.5) and further purification by column chromatography on silica gel (eluent: chloroform/methanol=100/0 to 99/1)

Sources & evidence

ORD record
ord-04c8341dd23a42458d178a063a32b187
Source dataset
uspto-grants-2008_08
Patent number
US07417060B2

Reaction notes

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