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

HRID 922707Notes

Reaction equation

HRID 922707 reaction equation
O[C:2]1([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[C:15]([C:20]([NH:22][CH3:23])=[O:21])[CH:14]=[CH:13]3)[C:9]2[N:5]([CH:6]=[N:7][CH:8]=2)[CH2:4][CH2:3]1.C([OH:26])C>>[OH:26][C:8]1[N:7]=[CH:6][N:5]2[CH2:4][CH2:3][C@@H:2]([C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[CH:16]=[C:15]([C:20]([NH:22][CH3:23])=[O:21])[CH:14]=[CH:13]4)[C:9]=12

Participants

3

Reactant 2

HCID 702Ethanol2×HCID 98830296-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-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 25%

Conditions

Temperature
50 °C

Procedure

6-(7-Hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (5.20 kg, 16.9 mol), ethanol (130 L) and activated carbon (260 g) were stirred at room temperature, and the insoluble material was filtered off, and washed with ethanol (15.6 L). The above-mentioned operations were repeated three times. The filtrates and washings were combined, and (2S,3S)-tartranilic acid (15.95 kg, 70.8 mol) and ethanol (20.8 L) were added thereto. The mixture was heated to about 50° C., allowed to cool to room temperature, stirred for about 4 hr, cooled to about 0° C., and stirred for about 1 hr. The precipitated crystals were collected by filtration, and washed with ethanol (31.2 L). The obtained wet crystals (about 23 kg) in ethanol (156 L) were stirred at room temperature for about 2 hr, and the mixture was cooled to about 0° C., and stirred for about 1 hr. The precipitated crystals were collected by filtration, and washed with ethanol (31.2 L). The obtained wet crystals (about 20 kg) were added to 1 mol/L aqueous sodium hydroxide solution (104 L), and the mixture was stirred at room temperature for about 1 hr. The precipitated crystals were collected by filtration, washed with water (93.6 L), and dried under reduced pressure to a constant amount to give 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide 1 hydrate (4.11 kg, 12.6 mol). yield 25%. containing 5.6 wt % water (by Karl-Fisher water measurement).

Workup

  1. filtrationthe insoluble material was filtered off
  2. washwashed with ethanol (15.6 L)
  3. temperatureto cool to room temperature
  4. temperaturecooled to about 0° C.
  5. stirringstirred for about 1 hr
  6. filtrationThe precipitated crystals were collected by filtration
  7. washwashed with ethanol (31.2 L)
  8. stirringThe obtained wet crystals (about 23 kg) in ethanol (156 L) were stirred at room temperature for about 2 hr
  9. temperaturethe mixture was cooled to about 0° C.
  10. stirringstirred for about 1 hr
  11. filtrationThe precipitated crystals were collected by filtration
  12. washwashed with ethanol (31.2 L)
  13. additionThe obtained wet crystals (about 20 kg) were added to 1 mol/L aqueous sodium hydroxide solution (104 L)
  14. stirringthe mixture was stirred at room temperature for about 1 hr
  15. filtrationThe precipitated crystals were collected by filtration
  16. washwashed with water (93.6 L)
  17. customdried under reduced pressure to a constant amount

Sources & evidence

ORD record
ord-984fe1d13b2c431d8876e03b446b5cae
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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