Allyl bromide → (6S)-N-Phenyl-3-[3-(trifluoromethyl)benzyl(benzyloxycarbonyl)amino]-4-oxo-8beta-allyl-8-methyl-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6alpha-carboxamide

HRID 481255Notes

Reaction equation

HRID 481255 reaction equation
[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:41])[C:16]([N:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:17][N:18]=[C:13]2[CH:12]([CH3:42])[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:43](Br)[CH:44]=C.[CH2:47]1COCC1>>[CH2:42]([C@@:12]1([CH3:47])[C:13]2=[N:18][CH:17]=[C:16]([N:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:15](=[O:41])[N:14]2[C@H:10]([C:8]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:9])[CH2:11]1)[CH:43]=[CH2:44]

Participants

4

Reactant 3

HCID 7841Allyl bromideHCID 8028Tetrahydrofuran2×HCID 86587570Benzyl (6S,8RS)-6-(anilinocarbonyl)-8-methyl-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidin-3-yl[3-(trifluoromethyl)benzyl]carbamate

Product 1

HCID 86587576(6S)-N-Phenyl-3-[3-(trifluoromethyl)benzyl(benzyloxycarbonyl)amino]-4-oxo-8beta-allyl-8-methyl-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6alpha-carboxamideYield 48%

Conditions

Temperature
-78 °C

Procedure

To a solution of 12c (2.155 g, 3.74 mmol) in 16 mL THF at −78° C., was added 1.0 M LIHMDS in THF (7.66 mL, 7.66 mmol). The mixture was stirred at −78° C. for 10 min, then allyl bromide (0.81 mL, 9.34 mmol) was added. The mixture was allowed to slowly warm to −40° C. and was maintained at this temperature for 30 min. The reaction was quenched with sat. NH4Cl, then diluted with EtOAc. The organic phase was washed with 0.5 M HCl and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography (40% EtOAc/hexanes) to afford 1.101 g (48%) of 117a as a colorless gum. MS (ESI) 617.2 (M+H+).

Workup

  1. temperatureto slowly warm to −40° C.
  2. temperaturewas maintained at this temperature for 30 min
  3. customThe reaction was quenched with sat. NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with 0.5 M HCl and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash chromatography (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-479c5772587a41f39c9ca7b4ba97f1bc
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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