Water → 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide

HRID 922728Notes

Reaction equation

HRID 922728 reaction equation
O[C@@:2]([C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH:27]=[C:26]([C:31]([NH:33][CH3:34])=[O:32])[CH:25]=[CH:24]2)([C:6]1[N:7]=[CH:8][N:9](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1)[CH2:3][CH2:4]O.C(N(C(C)C)C(C)C)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].[OH2:55]>C1COCC1>[OH:55][C:10]1[N:9]=[CH:8][N:7]2[CH2:4][CH2:3][C@@H:2]([C:21]3[CH:22]=[C:23]4[C:28](=[CH:29][CH:30]=3)[CH:27]=[C:26]([C:31]([NH:33][CH3:34])=[O:32])[CH:25]=[CH:24]4)[C:6]=12

Participants

7

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 867154076-[(1S)-1,3-dihydroxy-1-(1-tosyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide

Product 1

HCID 666510376-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamideYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To THF (4.8 mL) was added 6-[(1S)-1,3-dihydroxy-1-(1-tosyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (479.6 mg, 1.0 mmol). The reaction mixture was cooled to 10° C., and ethyldiisopropylamine (505.9 mg, 4.0 mmol) and methanesulfonyl chloride (458.8 mg, 4.0 mmol) were successively added thereto, and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added a solution of sodium carbonate (530.0 mg, 5.0 mmol) in water (2 mL), and the mixture was warmed to 57° C., and stirred for 5 hr. The separated organic layer was concentrated under reduced pressure. Methanol (4 mL) and activated carbon (40 mg) were added thereto. The reaction mixture was stirred at the same temperature for 20 min, and the activated carbon was filtered off, and washed with methanol (2 mL). The filtrate and washing were concentrated under reduced pressure. Methanol (1 mL), ethyl acetate (5 mL), and THF (10 mL) were added to the residue, and the mixture was washed twice with 10% sodium chloride-containing 5 w/v % aqueous sodium bicarbonate solution (15 mL). The separated organic layer was concentrated under reduced pressure to give 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (135.4 mg, 0.44 mmol). yield 44%.

Workup

  1. temperaturethe mixture was warmed to 57° C.
  2. stirringstirred for 5 hr
  3. concentrationThe separated organic layer was concentrated under reduced pressure
  4. additionMethanol (4 mL) and activated carbon (40 mg) were added
  5. stirringThe reaction mixture was stirred at the same temperature for 20 min
  6. filtrationthe activated carbon was filtered off
  7. washwashed with methanol (2 mL)
  8. washThe filtrate and washing
  9. concentrationwere concentrated under reduced pressure
  10. additionMethanol (1 mL), ethyl acetate (5 mL), and THF (10 mL) were added to the residue
  11. washthe mixture was washed twice with 10% sodium chloride-
  12. additioncontaining 5 w/v % aqueous sodium bicarbonate solution (15 mL)
  13. concentrationThe separated organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-93139261c9e441dfada11d8768f65706
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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