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

반응식

HRID 10986 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 67553Tetrabutylammonium Iodide촉매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-d0d4c49598e642f9a8b23b814d8fa918
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094783B2

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