Triethylamine → HCID 67148233, compound

HRID 2426267Notes

Reaction equation

HRID 2426267 reaction equation
C([O:9][C:10]1[C:21](=[O:22])[N:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19](Br)[C:13]2=[N:12][C:11]=1[C:23]([O:25][CH3:26])=[O:24])(=O)C1C=CC=CC=1.[C:27]1([C@H:33]([NH2:35])[CH3:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C>CN(C)C=O.CO.O>[OH:9][C:10]1[C:21](=[O:22])[N:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]([NH:35][C@@H:33]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH3:34])[C:13]2=[N:12][C:11]=1[C:23]([O:25][CH3:26])=[O:24]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6431891-Phenethylamine, (+)-2×HCID 67148260HCID 67148260, compound2×

Product 1

HCID 67148233HCID 67148233, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

Methyl 3-(benzoyloxy)-10-bromo-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepine-2-carboxylate (1.0 eq.) was added to a solution of (1R)-1-phenylethylamine (2.2 eq.) and triethylamine (1 eq) dissolved in N,N-dimethylformamide. The mixture was stirred vigorously for 2 hours at room temperature and then at 50° C. for 30 minutes. The solvent was removed under reduced pressure and the title crude product (a mixture 1:1 of diastereoisomers) for use without further purification. In an alternative procedure (Step 5A), solid methyl 3-(benzoyloxy)-10-bromo-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepine-2-carboxylate (1.0 eq.) was added to a solution of (1R)-1-phenylethylamine (4.5 eq.) dissolved in a 7:3 methanol/water mixture at −30° C. The reaction was carried out over night, then the temperature was raised to room temperature and the solvent concentrated to obtain a white solid that was filtered off and discarded. The title compound (as a mixture 7:3 of diastereoisomers) was extracted in dichloromethane from the mother liquid for use in the next step without further purification.

Workup

  1. waitat 50° C. for 30 minutes
  2. customThe solvent was removed under reduced pressure
  3. customthe title crude product (a mixture 1:1 of diastereoisomers) for use without further purification
  4. waitThe reaction was carried out over night
  5. temperaturethe temperature was raised to room temperature
  6. concentrationthe solvent concentrated
  7. customto obtain a white solid
  8. filtrationthat was filtered off
  9. extractionThe title compound (as a mixture 7:3 of diastereoisomers) was extracted in dichloromethane from the mother liquid for use in the next step without further purification

Sources & evidence

ORD record
ord-46102c9d49b0436a9e5333e0bb1f1dd7
Source dataset
uspto-grants-2011_06
Patent number
US07968553B2

Reaction notes

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