Triethylamine → 3-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)-N-(3-isopropylphenyl)benzamide

HRID 1052076Notes

Reaction equation

HRID 1052076 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[N:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O.C(N(CC)CC)C.CCCP(=O)=O.[CH:33]([C:36]1[CH:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39])([CH3:35])[CH3:34]>CN(C1C=CN=CC=1)C.ClCCCl>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[N:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([NH:39][C:38]1[CH:40]=[CH:41][CH:42]=[C:36]([CH:33]([CH3:35])[CH3:34])[CH:37]=1)=[O:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4586793-Isopropylaniline2×HCID 16167369Propylphosphoric anhydride2×HCID 866958783-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)benzoic acid

Product 1

HCID 717361753-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)-N-(3-isopropylphenyl)benzamideYield 59.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of 3-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)benzoic acid (15.0 mg, 0.059 mmol), triethylamine (0.016 mL, 0.12 mmol) and catalytic DMAP in 1.0 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.046 mL, 0.077 mmol). After 8 min at rt, 3-isopropylaniline (0.015 mL, 0.106 mmol) was added and the reaction stirred at rt for 18 hours. Then additional 3-isopropylaniline (0.015 mL) and propylphosphonic anhydride solution (0.030 mL) was added and the reaction continued for an additional 3 hours. The reaction was quenched into brine/dilute aqueous Na2CO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, brine/dilute aqueous Na2CO3 solution, dried with anhydrous Na2SO4 and rotary evaporated to an oil. The oil was chromatographed eluting with CHCl3/EtOAc to give the title compound as a light yellow solid (13 mg, 57%). 1H NMR (CDCl3) δ: 8.42 (s, 1H), 8.38 (d, J=5.0 Hz, 1H), 7.94 (s, 1H), 7.55-7.57 (m, 2H), 7.47 (ddd, J=8.1, 2.2, 1.2 Hz, 1H), 7.34-7.40 (m, 1H), 7.29 (t, J=7.8 Hz, 1H), 7.21-7.26 (m, 1H), 7.08-7.14 (m, 2H), 7.01-7.05 (m, 1H), 4.46 (s, 2H), 3.63 (t, J=5.9 Hz, 2H), 2.85-3.02 (m, 3H), 1.27 (d, J=7.0 Hz, 6H).

Workup

  1. waitthe reaction continued for an additional 3 hours
  2. customThe reaction was quenched into brine/dilute aqueous Na2CO3 solution
  3. extractionextracted with EtOAc
  4. washthe EtOAc layer washed with H2O, brine/dilute aqueous Na2CO3 solution
  5. dry with materialdried with anhydrous Na2SO4
  6. customrotary evaporated to an oil
  7. customThe oil was chromatographed
  8. washeluting with CHCl3/EtOAc

Sources & evidence

ORD record
ord-73e3c70639f64acca7cb1809487a7823
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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