3-Methyl-2-furoic acid → HCID 178497206, compound

HRID 2203288Notes

Reaction equation

HRID 2203288 reaction equation
CC1C=CO[C:3]=1[C:7]([OH:9])=O.[CH:10]([N:13]([CH2:17]C)[CH:14](C)[CH3:15])(C)[CH3:11].F[P-](F)(F)(F)(F)F.[N:26]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:46][NH:47][C:48]1[CH:53]=[CH:52][C:51]([CH:54]2[CH2:72][N:58]3[C:59](=[O:71])[NH:60][C:61]4[CH:62]=[C:63]([C:67]([O:69][CH3:70])=[O:68])[CH:64]=[CH:65][C:66]=4[C:57]3=[N:56][CH2:55]2)=[CH:50][CH:49]=1>CN(C=O)C>[CH3:46][N:47]([C:7](=[O:9])[CH2:3][N:26]1[CH2:15][CH2:14][N:13]([CH3:17])[CH2:10][CH2:11]1)[C:48]1[CH:49]=[CH:50][C:51]([CH:54]2[CH2:72][N:58]3[C:59](=[O:71])[NH:60][C:61]4[CH:62]=[C:63]([C:67]([O:69][CH3:70])=[O:68])[CH:64]=[CH:65][C:66]=4[C:57]3=[N:56][CH2:55]2)=[CH:52][CH:53]=1

Participants

6

Reactant 4

HCID 781273-Methyl-2-furoic acid2×HCID 81531Diisopropylethylamine2×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2×HCID 178482093HCID 178482093, compound

Product 1

HCID 178497206HCID 178497206, compoundYield 31.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-methyl-furan-2-carboxylic acid (1.9 mg, 0.012 mmol), N,N-diisopropylethylamine (0.0064 mL, 0.037 mmol), and BOP (5.7 mg, 0.013 mmol) in 0.35 mL DMF was stirred at rt for 20 minutes, then methyl 3-[4-(methylamino)phenyl]-6-oxo-3,4,6,7-tetrahydro-2H-pyrimido[1,2-c]quinazoline-9-carboxylate (3.7 mg, 0.010 mmol) added and the reaction continued at rt. After 19 hours, the reaction was heated at 60° C. for 23 hours, then added a small spatula tip of 3-methyl-furan-2-carboxylic acid and BOP plus 0.015 mL N,N-diisopropylethylamine and continued heating at 80° C. for an additional 4 hours. The reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and evaporated. The resulting yellow oil was chromatographed on a prep plate eluting with 20% MeOH/CHCl3 plus NH4OH. The obtained oily solid was then triturated with EtOAc/hexane to give the title compound as an off-white solid (1.6 mg, 31%). 1H NMR (CD3OD/CDCl3 mixture) δ: 8.14 (d, J=8.2 Hz, 1H), 7.76 (dd, J=8.2, 1.5 Hz, 1H), 7.69 (d, J=0.9 Hz, 1H), 7.41 (d, J=7.9 Hz, 2H), 7.28 (d, J=8.5 Hz, 2H), 4.49 (dt, J=12.6, 3.7 Hz, 1H), 3.96 (s, 4H), 3.66-3.76 (m, 2H), 3.28 (s, 3H), 3.17-3.24 (m, 1H), 3.05 (br. s, 2H), 2.92 (br. s, 4H), 2.62 (br. s, 7H).

Workup

  1. customcontinued at rt
  2. waitAfter 19 hours
  3. temperaturethe reaction was heated at 60° C. for 23 hours
  4. temperaturecontinued heating at 80° C. for an additional 4 hours
  5. customThe reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  6. washthe EtOAc layer washed with H2O, brine
  7. dry with materialdried with anhydrous Na2SO4
  8. customevaporated
  9. customThe resulting yellow oil was chromatographed on a prep plate
  10. washeluting with 20% MeOH/CHCl3 plus NH4OH
  11. customThe obtained oily solid was then triturated with EtOAc/hexane

Sources & evidence

ORD record
ord-516d781509604342b941cab37fe8f8ba
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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