HCID 22725143, compound → HCID 69874997, compound

HRID 2085418Notes

Reaction equation

HRID 2085418 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[N:14]([C:15]([O:17]C3C=CC([N+]([O-])=O)=CC=3)=O)[C:13]([O:27][CH3:28])=[N:12][C:11]([CH2:29][CH3:30])=[C:10]2[C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH:5]=[CH:6][C:7]=1[F:8]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[N:14]([C:15]([NH:14][C@@H:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=3)[CH3:10])=[O:17])[C:13]([O:27][CH3:28])=[N:12][C:11]([CH2:29][CH3:30])=[C:10]2[C:31]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[O:32])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 1

HCID 22725143HCID 22725143, compound

Product 1

HCID 69874997HCID 69874997, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a stirred mixture of 5-benzyl 1-(4-nitrophenyl) 6-(3,4-difluorophenyl)-4-ethyl-2-methoxy-1,5(6H)-pyrimidinedicarboxylate (12.6 g, 22.86 mmol) in THF (150 mL) was added a solution of R-(+)-α-methyl benzylamine (3.53 mL, 27.44 mmol) at room temperature. The stirring was continued for 12 h and the solvent was removed in vacuo. The yellow residue was dissolved in chloroform (200 mL) and was washed with 10% K2CO3 solution (2×30 mL). The organic layer was dried over Na2SO4, filtered and the solvent was removed in vacuo. The resulting mixture of diastereomers was separated by column chromatography over silica gel with 9:1 pet. ether:ether to 4:1 pet. ether:ether. First major product to elute was (+)-benzyl 6-(3,4-difluorophenyl)-4-ethyl-2-methoxy-1-({[(1R)-1-phenylethyl]amino}carbonyl)-1,6-dihydro-5-pyrimidinecarboxylate: Colorless oil, Rf=0.31(4:1 pet ether:ether); wt.=3.8 g (60% yield); [α]D=+267.05 (c=0.76, CHCl3); 1H NMR (CDCl3) δ 1.22 (t, J=7.5 Hz, 3H), 1.52 (d, J=6.9 Hz, 3H), 2.88 (q, J=6.0 Hz, 2H), 3.99 (s, 3H), 4.99 (m, 1H), 5.09 (ABq, 2H), 6.66 (s, 1H), 6.99-7.36 (m, 13H); The second major product to elute was (−)-benzyl 6-(3,4-difluorophenyl)-4-ethyl-2-methoxy-1-({[(1R)-1-phenylethyl]amino}carbonyl)-1,6-dihydro-5-pyrimidinecarboxylate: Colorless oil; Rf=0.22 (4:1 pet ether:ether); wt.=3.2 g (51.2% yield); [α]D=−146.89 (c=0.38, CHCl3); 1H NMR (CDCl3) δ 1.22 (t, J=7.2 Hz, 3H), 1.49 (d, J=6.6 Hz, 3H), 2.88 (q, J=6.0 Hz, 2H), 3.94 (s, 3H), 5.03 (m, 1H), 5.11 (ABq, 2H), 6.68 (s, 1H) 6.91-7.34 (m, 13H).

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe yellow residue was dissolved in chloroform (200 mL)
  3. washwas washed with 10% K2CO3 solution (2×30 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. additionThe resulting mixture of diastereomers
  8. customwas separated by column chromatography over silica gel with 9:1 pet. ether
  9. washFirst major product to elute
  10. washThe second major product to elute

Sources & evidence

ORD record
ord-02cfcab8d6cc4d788136bb2ac7a937e1
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

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