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

HRID 481249Notes

Reaction equation

HRID 481249 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.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CC(C1C=C(C(C)C)C(S([N:68]=[N+:69]=[N-:70])(=O)=O)=C(C(C)C)C=1)C.CC(O)=O>C1COCC1.CCOC(C)=O>[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[C@@:12]([N:68]=[N+:69]=[N-:70])([CH3:42])[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 2733832Lithium HexamethyldisilazideHCID 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 101334627(6S)-N-Phenyl-3-[3-(trifluoromethyl)benzyl(benzyloxycarbonyl)amino]-4-oxo-8beta-azido-8-methyl-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6alpha-carboxamideYield 71.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the methyl diastereomers (12c) (1.02 g, 1.78 mmol) in 10 mL THF at −78° C., was added LiHMDS (1M in THF, 3.73 mL, 3.73 mmol). The red solution was stirred at −78° C. for 10 min, then a solution of trisyl azide (606 mg, 1.96 mmol) in 2 mL THF was added. The reaction was stirred at −78° C. for 1.5 h, then was quenched with the addition of AcOH (459 μL, 8.01 mmol). The mixture was stirred at rt for 1 h, then was diluted with EtOAc. The organic phase was washed with sat. NH4Cl and brine, dried (Na2SO4), and concentrated. The product was purified by flash chromatography (30 to 35% EtOAc/hexanes) to afford 784 mg (71%) of azide (12d). 1H NMR (300 MHz, CDCl3) δ9.26 (br s, 1H), 7.82 (br s, 1H), 7.51-7.25 (m, 13H), 7.10 (t, J=7.3, 1H), 5.23 (m, 3H), 4.91-4.77 (m, 2H), 2.90 (d, J=13.9, 1H), 2.43 (dd, J=13.6, 9.2, 1H), 1.87 (s, 3H); MS (ESI) 640.4 (M+Na+), 616.4 (M−H+).

Workup

  1. stirringThe reaction was stirred at −78° C. for 1.5 h
  2. stirringThe mixture was stirred at rt for 1 h
  3. washThe organic phase was washed with sat. NH4Cl and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography (30 to 35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-40aa03b63c7b487dadf5a930431dc6f4
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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