Dimethylformamide → HCID 19787904, compound

HRID 1656535Notes

Reaction equation

HRID 1656535 reaction equation
N[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([NH:12][CH:13]([CH:20]([CH3:22])[CH3:21])[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])=[O:11])[C:5]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[N:4][CH:3]=1.[CH:30]([N:33]=[C:34]=[O:35])([CH3:32])[CH3:31].CN(C)C=O.C(N(CC)CC)C>O1CCCC1.ClCCl.C(OCC)C>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:5]2[N:6]([CH2:9][C:10]([NH:12][CH:13]([CH:20]([CH3:21])[CH3:22])[C:14](=[O:19])[C:15]([F:16])([F:17])[F:18])=[O:11])[C:7](=[O:8])[C:2]([C:34]([NH:33][CH:30]([CH3:32])[CH3:31])=[O:35])=[CH:3][N:4]=2)=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 61277Isopropyl isocyanate3×HCID 10024782HCID 10024782, compound

Product 1

HCID 19787904HCID 19787904, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of 2-[5-amino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (0.414 g) in dry tetrahydrofuran (3 mL) and dichloromethane (5 mL) was added isopropyl isocyanate (110 uL). After overnight stiring, dimethylformamide (1.5 mL), triethylamine (100 uL) and isopropyl isocyanate (50 uL) were added. The reaction mixture was heated to reflux for 24 h. The mixture was cooled to room temperature and cuprous chloride (120 mg) followed by three portions of isopropyl isocyanate (50 uL, 50 uL, and 25 uL) were added. The reaction mixture was diluted with diethyl ether and rinsed with dilute hydrochloric acid and brine. The organic phase was dried and evaporated to afford an oil which was purified by chromatography, with chloroform:methanol (gradient 100:0, 97:3) as the eluent. This afforded 160 mg of a yellow-green solid. Analysis by NMR showed line broadening, indicative of contamination by a heavy metal. The remaining 135 mg sample was dissolved in methyl tert-butyl ether and rinsed with 5% disodium EDTA solution followed by dilute aqueous ammonia. The organic phase was dried and evaporated to afford the title compound (120 mg) as an off-white powder; TLC: Rf =0.46, chloroform:methanol (9:1); NMR: 8.62 (s,1), 7.52 (dd,2), 7.26 (dd,2), 4.6 (dd,2), 4.04 (d,1), 2.25 (m,1), 1.09 (d,6), 0.85 (d,3), 0.76 (d,3); MS: m/z=500(M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 h
  3. additionwere added
  4. washrinsed with dilute hydrochloric acid and brine
  5. customThe organic phase was dried
  6. customevaporated
  7. customto afford an oil which
  8. customwas purified by chromatography, with chloroform
  9. dissolutionThe remaining 135 mg sample was dissolved in methyl tert-butyl ether
  10. washrinsed with 5% disodium EDTA solution
  11. customThe organic phase was dried
  12. customevaporated

Sources & evidence

ORD record
ord-56d40962f0c745809b13f281666228f5
Source dataset
uspto-grants-1993_10
Patent number
US05254558

Reaction notes

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