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

HRID 481248Notes

Reaction equation

HRID 481248 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)[C:12]1[C:17](=[O:18])[N:16]2[C@H:19]([C:22]([OH:24])=O)[CH2:20][CH2:21][C:15]2=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1C=NC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+].CCN=C=NCCCN(C)C>CCOC(C)=O.C(Cl)Cl.CN(C=O)C>[NH:36]([C:22]([C@H:19]1[N:16]2[C:17](=[O:18])[C:12]([N:11]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:34])([F:33])[F:35])[CH:27]=3)[C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:13][N:14]=[C:15]2[CH2:21][CH2:20]1)=[O:24])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 5

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 57444827(S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic Acid

Product 1

HCID 86587567(6S)-N-Phenyl-3-[3-(trifluoromethyl)benzyl(benzyloxycarbonyl)amino]-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6alpha-carboxamide

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of 12a (6.18 g, 12.7 mmol) and aniline (1.64 mL, 19.0 mmol) in 60 mL 5:1 CH2Cl2/DMF at 0° C., was added HOAt (1.90 g, 14.0 mmol), NaHCO3 (2.13 g, 25.4 mmol), and EDCI (3.41 g, 17.8 mmol). The mixture was stirred and allowed to warm to rt over 15 h. The reaction was diluted with EtOAc and the organic phase was washed with H2O, sat. NaHCO3, H2O, 1N HCl, H2O, and brine. The organic phase was dried (Na2SO4) and concentrated. The residue obtained was purified by flash chromatography (50 to 60 to 70% EtOAc/hexanes) to afford 4.60 g (60%, 2 steps) of 12b as an off-white solid. 1H NMR (300 MHz, CDCl3) δ9.35 (br s, 1H), 7.68 (br s, 1H), 7.52-7.21 (m, 13H), 7.07 (t, J=7.5, 1H), 5.28 (dd, J=8.7, 0.5, 1H), 5.22-5.11 (m, 2H), 4.84 (br s, 2H), 3.47-3.34 (m, 1H), 3.04-2.95 (m, 1H), 2.80 (br t, J=10.5, 1H), 2.44-2.30 (m, 1H). MS (ESI) 563.5 (M+H+), 35 585.5 (M+Na+), 561.4 (M−H+).

Workup

  1. washthe organic phase was washed with H2O, sat. NaHCO3, H2O, 1N HCl, H2O, and brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue obtained
  5. customwas purified by flash chromatography (50 to 60 to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-01a2c7a0b7784541b043db758d1b1e81
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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