3-Methyl-2-furoic acid → HCID 178428788, compound

HRID 2203283Notes

Reaction equation

HRID 2203283 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([OH:9])=O.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:46][C:47]1[CH:48]=[C:49]([CH:53]2[CH2:67][N:57]3[C:58](=[O:66])[NH:59][C:60]4[CH:61]=[CH:62][CH:63]=[CH:64][C:65]=4[C:56]3=[N:55][CH2:54]2)[CH:50]=[CH:51][CH:52]=1>CN(C=O)C>[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([NH:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([CH:53]2[CH2:67][N:57]3[C:58](=[O:66])[NH:59][C:60]4[CH:61]=[CH:62][CH:63]=[CH:64][C:65]=4[C:56]3=[N:55][CH2:54]2)[CH:48]=1)=[O:9]

Participants

6

Reactant 4

HCID 781273-Methyl-2-furoic acid2×HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate2×HCID 178507527HCID 178507527, compound

Product 1

HCID 178428788HCID 178428788, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-methyl-furan-2-carboxylic acid (2.4 mg, 0.019 mmol), N,N-diisopropylethylamine (0.017 mL, 0.095 mmol), and BOP (10.1 mg, 0.023 mmol) in 0.6 mL DMF was stirred at rt for 1 hour, then 3-(3-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (5.0 mg, 0.017 mmol) added and the reaction continued at rt. After 2.5 hours, a small spatula tip of 3-methyl-furan-2-carboxylic acid and BOP was added and the reaction heated at 60° C. for 1 hour. The reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The residue was rinsed with 2 portions of 30% EtOAc/hexane and then chromatographed eluting with 10% MeOH/CHCl3. The resulting solid was chromatographed using a prep plate and eluting with 50% acetone/hexane. The obtained solid was then partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and evaporated to give the title compound as a white solid (3.2 mg, 47%). 1H NMR (CD3OD/CDCl3 mixture) δ: 8.04 (dd, J=8.2, 1.2 Hz, 1H), 7.68 (t, J=1.8 Hz, 1H), 7.60 (ddd, J=8.1, 2.1, 0.9 Hz, 1H), 7.46-7.53 (m, 2H), 7.37 (t, J=7.9 Hz, 1H), 7.16 (ddd, J=8.1, 7.2, 1.2 Hz, 1H), 7.03-7.10 (m, 2H), 6.45 (dd, J=1.8, 0.6 Hz, 1H), 4.48-4.56 (m, 1H), 3.86-3.95 (m, 1H), 3.61-3.74 (m, 2H), 3.07-3.19 (m, 1H), 2.42 (s, 3H).

Workup

  1. customcontinued at rt
  2. waitAfter 2.5 hours
  3. temperaturethe reaction heated at 60° C. for 1 hour
  4. customThe reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  5. washthe EtOAc layer washed with H2O, brine
  6. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  7. washThe residue was rinsed with 2 portions of 30% EtOAc/hexane
  8. customchromatographed
  9. washeluting with 10% MeOH/CHCl3
  10. customThe resulting solid was chromatographed
  11. washeluting with 50% acetone/hexane
  12. customThe obtained solid was then partitioned between EtOAc and aqueous Na2CO3 solution
  13. washthe EtOAc layer washed with H2O, brine
  14. dry with materialdried with anhydrous Na2SO4
  15. customevaporated

Sources & evidence

ORD record
ord-fef13767a2224c9f96e2826b0b9023d3
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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