4-Propylaniline → 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-N-(4-propylphenyl)benzamide

HRID 1051996Notes

Reaction equation

HRID 1051996 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15](O)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1.[CH2:21]([C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1)[CH2:22][CH3:23].C(N(CC)C(C)C)(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([NH:28][C:27]3[CH:29]=[CH:30][C:24]([CH2:21][CH2:22][CH3:23])=[CH:25][CH:26]=3)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 759084-PropylanilineHCID 81531DiisopropylethylamineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 866958153-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid

Product 1

HCID 717355273-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-N-(4-propylphenyl)benzamideYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (41 mg, 0.15 mmol), 4-propylaniline (0.029 mL, 0.20 mmol), and N,N-diisopropylethylamine (0.052 mL, 0.30 mmol) in 1.5 mL DMF at room temperature was added COMU (68 mg, 0.158 mmol). The reaction was briefly warmed to approx. 60° C. and then continued at room temperature for 15 hours. The reaction was added drop wise to a stirring mixture of 35 mL water containing 5 mL brine at room temperature, and the resulting precipitate filtered and rinsed with water. The filtrate 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 combined with the filtered precipitate and then chromatographed eluting with portions of CHCl3, then 1:1 CHCl3:EtOAc, and then 5% MeOH/CHCl3. The obtained solid was then triturated with an EtOAc/hexane mixture to give the title compound as a light beige solid (18 mg, 32%). 1H NMR (DMSO-d6) δ: 10.07 (s, 1H), 8.13 (s, 1H), 7.62-7.69 (m, 2H), 7.48-7.51 (m, 1H), 7.31-7.40 (m, 2H), 7.21 (dt, J=7.7, 2.0 Hz, 1H), 7.13-7.19 (m, 2H), 6.40 (s, 2H), 4.29 (s, 2H), 3.65 (t, J=6.0 Hz, 2H), 2.77 (t, J=5.9 Hz, 2H), 2.50-2.56 (m, 2H), 1.58 (sxt, J=7.4 Hz, 2H), 0.89 (t, J=7.3 Hz, 3H).

Workup

  1. additionThe reaction was added drop
  2. filtrationthe resulting precipitate filtered
  3. washrinsed with water
  4. customThe filtrate 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. customchromatographed
  8. washeluting with portions of CHCl3
  9. customThe obtained solid was then triturated with an EtOAc/hexane mixture

Sources & evidence

ORD record
ord-f8310f0408534bb984270a762fa5cbda
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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