Tetrahydrofuran → (S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic Acid

HRID 10986

Reaction equation

HRID 10986 reaction equation
[CH2:1]([O:8][C:9](=[O:41])[NH:10][C:11]1[C:16](=[O:17])[N:15]2[CH:18]([C:21](=[O:40])NCC3C=CC(C(NC(OC(C)(C)C)=O)=N)=CC=3)[CH2:19][CH2:20][C:14]2=[N:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:42][C:43]([F:53])([F:52])[C:44]1[CH:45]=[C:46]([CH:49]=[CH:50][CH:51]=1)[CH2:47]Br.[H-].[Na+].C1C[O:59]CC1>CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH2:1]([O:8][C:9]([N:10]([CH2:47][C:46]1[CH:49]=[CH:50][CH:51]=[C:44]([C:43]([F:53])([F:52])[F:42])[CH:45]=1)[C:11]1[C:16](=[O:17])[N:15]2[C@H:18]([C:21]([OH:59])=[O:40])[CH2:19][CH2:20][C:14]2=[N:13][CH:12]=1)=[O:41])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 145857201benzyl N-[6-[[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenyl]methylcarbamoyl]-4-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidin-3-yl]carbamate

Product 1

HCID 57444827(S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic AcidYield 93%

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

To a mixture of acid 1i (4.50 g, 13.7 mmol) in 70 mL THF at 0° C., was added 3-(trifluoromethyl)benzyl bromide (8.35 mL, 54.7 mmol), NaH (60% dispersion in oil, 1.64 g, 41.4 mmol), and TBAI (100 mg, catalytic). The reaction was stirred at rt for 15 h, then quenched with the addition of 50 mL H2O. The volatile solvents were removed by rotary evaporation and the aqueous solution obtained was partitioned with Et2O. The organic phase was extracted with 20% sat. NaHCO3 (3×). The combined aqueous extract was acidified with 1N HCl and extracted with EtOAc (5×). The combined organic extract was washed (brine), dried (Na2SO4), and concentrated to afford 6.18 g (93%) of the 3-(trifluoromethyl)benzyl amine (25a), which was used in the following step without additional purification. MS (ESI) 488.3 (M+H+), 510.3 (M+Na+); 486.3 (M−H+).

Workup

  1. customquenched with the addition of 50 mL H2O
  2. customThe volatile solvents were removed by rotary evaporation
  3. customthe aqueous solution obtained
  4. customwas partitioned with Et2O
  5. extractionThe organic phase was extracted with 20% sat. NaHCO3 (3×)
  6. extractionThe combined aqueous extract
  7. extractionextracted with EtOAc (5×)
  8. extractionThe combined organic extract
  9. washwas washed (brine)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d0d4c49598e642f9a8b23b814d8fa918
Source dataset
uspto-grants-2006_08
Patent number
US07094783B2

Linked notes

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