Triethylamine → HCID 19390791, compound

HRID 1756708Notes

Reaction equation

HRID 1756708 reaction equation
[NH2:1][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([NH:12][CH:13]([CH:30]([CH3:32])[CH3:31])[C:14](=[O:29])[C:15]([F:28])([F:27])[C:16](=[O:26])[NH:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:11])[C:5]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:4][CH:3]=1.C(N(CC)CC)C.Cl[C:47](Cl)([O:49][C:50](=[O:56])OC(Cl)(Cl)Cl)Cl.[N:58]1[CH:63]=[CH:62][C:61](CO)=[CH:60][CH:59]=1>O1CCCC1.C(OCC)(=O)C.CO.ClCCl>[O:8]=[C:7]1[N:6]([CH2:9][C:10]([NH:12][CH:13]([CH:30]([CH3:32])[CH3:31])[C:14](=[O:29])[C:15]([F:28])([F:27])[C:16](=[O:26])[NH:17][CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:11])[C:5]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:4][CH:3]=[C:2]1[NH:1][C:50]([O:49][CH2:47][C:61]1[CH:62]=[CH:63][N:58]=[CH:59][CH:60]=1)=[O:56]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 114724-HydroxymethylpyridineHCID 94429TriphosgeneHCID 19390786HCID 19390786, compound

Product 1

HCID 19390791HCID 19390791, compoundYield 89.8%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

2-(5-Amino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)-N-[3,3-difluoro-1-isopropyl-2-oxo-3-(N-phenethylcarbamoyl)propyl]acetamide (0.140 g) in tetrahydrofuran (2 mL) was cooled in a salt/ice-water bath. After triethylamine (0.045 mL) was added, a solution of triphosgene (0.030 g) in tetrahydrofuran (0.5 mL) was added dropwise. Two 0.5 mL rinses of the syringe were also added to the reaction mixture. The mixture was stirred in a salt/ice-water bath for 40 minutes. Solid 4-pyridylcarbinol (0.058 g) was added and the mixture was allowed to slowly warm to room temperature. Tetrahydrofuran (1.5 mL) was added to the solution and it was allowed to stir overnight. The mixture was diluted with ethyl acetate and washed with saturated bicarbonate. The organic phase was washed with brine, dried and evaporated to give an oil. Chromatography, with dichloromethane:methanol (gradient, 98:2 to 95:5 to 90:10) as the eluent, followed by drying under vacuum, gave the title compound as a white solid (0.06 g); TLC: Rf =0.45, methanol:dichloromethane (10:90); 300 MHz NMR (DMSO/trifluoroacetic acid): 0.77 (d,3), 0.89 (d,3), 2.20-2.40 (m,1), 2.80 (t,2), 3.33-3.45 (m,2), 4.64 (q,2), 4.87 (d,1), 5.57 (s,2), 7.20-7.32 (m,5), 7.47-7.62 (m,5), 8.23 (d,2 ), 8.56 (s,1), 9.00 (d,2), 9.25 (t,1); MS: m/z=661 (M+1). Analysis for C34H34F2N6O6 : Calculated: C, 61.81; H, 5.19; N, 12.72; Found: C, 62.07; H, 5.47; N, 12.67.

Workup

  1. washwashed with saturated bicarbonate
  2. washThe organic phase was washed with brine
  3. customdried
  4. customevaporated
  5. customto give an oil
  6. customby drying under vacuum

Sources & evidence

ORD record
ord-d284acccca4046449ea16fff08d77cb8
Source dataset
uspto-grants-1995_08
Patent number
US05441960

Reaction notes

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