4-Isopropylaniline → HCID 118699723, compound

HRID 1773312Notes

Reaction equation

HRID 1773312 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:5]([O:27][CH3:28])=[CH:6][C:7]2[C:16]3[CH2:15][CH2:14][N:13]([C:17]4[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=4)[C:20](O)=[O:21])[CH2:12][C:11]=3[CH:10]=[N:9][C:8]=2[CH:26]=1.C(N(CC)C(C)C)(C)C.CCCP(=O)=O.[CH:44]([C:47]1[CH:53]=[CH:52][C:50]([NH2:51])=[CH:49][CH:48]=1)([CH3:46])[CH3:45]>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:2][O:3][C:4]1[C:5]([O:27][CH3:28])=[CH:6][C:7]2[C:16]3[CH2:15][CH2:14][N:13]([C:17]4[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=4)[C:20]([NH:51][C:50]4[CH:52]=[CH:53][C:47]([CH:44]([CH3:46])[CH3:45])=[CH:48][CH:49]=4)=[O:21])[CH2:12][C:11]=3[CH:10]=[N:9][C:8]=2[CH:26]=1

Participants

7

Reactant 4

HCID 74644-Isopropylaniline2×HCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydride2×HCID 118699725HCID 118699725, compound

Product 1

HCID 118699723HCID 118699723, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-(8,9-dimethoxy-1,4-dihydrobenzo[c]-2,7-naphthyridin-3(2H)-yl)benzoic acid hydrochloride (0.38 mmol, 152 mg), N, N-diisopropylethylamine (1.14 mmol, 0.199 mL), and catalytic DMAP in 2.0 mL DMF at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.494 mmol, 0.293 mL). After 8 min at rt, 4-isopropylaniline (0.57 mmol, 0.081 mL) was added and the reactions continued for 1.8 hours. Then an additional 0.050 mL propylphosphonic anhydride solution and 0.020 mL 4-isopropylaniline was added, the mixture briefly heated to 80° C. 3 times, and then continued at rt for 2 hours. The reaction was quenched into dilute aqueous Na2CO3 solution, extracted into EtOAc, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting solid was chromatographed eluting with CHCl3/EtOAc/MeOH and then triturated with EtOAc to give the title compound as a light yellow solid (23 mg, 13%).

Workup

  1. waitthe reactions continued for 1.8 hours
  2. wait3 times, and then continued at rt for 2 hours
  3. customThe reaction was quenched into dilute aqueous Na2CO3 solution
  4. extractionextracted into EtOAc
  5. washthe EtOAc layer washed with H2O, brine
  6. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  7. customThe resulting solid was chromatographed
  8. washeluting with CHCl3/EtOAc/MeOH
  9. customtriturated with EtOAc

Sources & evidence

ORD record
ord-9a53af77cada426abe269bdde17c3bb1
Source dataset
uspto-grants-2016_02
Patent number
US09255096B1

Reaction notes

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