3-Methyl-2-furoic acid → HCID 178428787, compound

HRID 2203284Notes

Reaction equation

HRID 2203284 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.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:43][C:44]1[CH:49]=[CH:48][C:47]([CH:50]2[CH2:64][N:54]3[C:55](=[O:63])[NH:56][C:57]4[CH:58]=[CH:59][CH:60]=[CH:61][C:62]=4[C:53]3=[N:52][CH2:51]2)=[CH:46][CH:45]=1>CN(C=O)C>[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([NH:43][C:44]1[CH:49]=[CH:48][C:47]([CH:50]2[CH2:64][N:54]3[C:55](=[O:63])[NH:56][C:57]4[CH:58]=[CH:59][CH:60]=[CH:61][C:62]=4[C:53]3=[N:52][CH2:51]2)=[CH:46][CH:45]=1)=[O:9]

Participants

6

Reactant 4

HCID 781273-Methyl-2-furoic acid2×HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 178507413HCID 178507413, compound

Product 1

HCID 178428787HCID 178428787, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-methyl-furan-2-carboxylic acid (3.7 mg, 0.029 mmol), N,N-diisopropylethylamine (0.025 mL, 0.145 mmol), and HBTU (13.2 mg, 0.035 mmol) in 0.8 mL DMF was stirred at rt for 10 minutes, then 3-(4-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (7.6 mg, 0.026 mmol) added and the reaction continued at rt. After 40 min, a spatula tip of 3-methyl-furan-2-carboxylic acid and HBTU was added, the reaction briefly warmed to approximately 60° C. several times, then allowed to cool to rt. At 1.25 hours 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 resulting solid was chromatographed on a prep plate eluting with 15% MeOH/CHCl3. The obtained solid was then partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated to give the title compound as an off-white solid (7.6 mg, 86%). 1H NMR (CD3OD/CDCl3 mixture) δ: 8.03 (dd, J=7.9, 1.2 Hz, 1H), 7.65-7.71 (m, 2H), 7.43-7.52 (m, 2H), 7.26-7.32 (m, 2H), 7.14 (ddd, J=8.1, 7.2, 1.2 Hz, 1H), 7.00-7.05 (m, 1H), 6.45 (d, J=1.5 Hz, 1H), 4.45 (ddd, J=13.0, 4.4, 2.8 Hz, 1H), 3.83-3.91 (m, 1H), 3.59-3.70 (m, 2H), 3.04-3.16 (m, 1H), 2.42 (s, 3H)

Workup

  1. customcontinued at rt
  2. waitAfter 40 min
  3. customthe reaction
  4. temperaturebriefly warmed to approximately 60° C. several times
  5. temperatureto cool to rt
  6. customAt 1.25 hours the reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  7. washthe EtOAc layer washed with H2O, brine
  8. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  9. customThe resulting solid was chromatographed on a prep plate
  10. washeluting with 15% MeOH/CHCl3
  11. customThe obtained solid was then partitioned between EtOAc and aqueous Na2CO3 solution
  12. washthe EtOAc layer washed with H2O, brine
  13. dry with materialdried with anhydrous Na2SO4
  14. customrotary evaporated

Sources & evidence

ORD record
ord-6f5776529ade4471afb5f010d7c70481
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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