Triethylamine → N-(3-hydroxypropyl)-7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxamide

HRID 338776Notes

Reaction equation

HRID 338776 reaction equation
[CH:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([N:19]3[CH2:28][C:27]4[CH:26]=[N:25][CH:24]=[C:23]([C:29](O)=[O:30])[C:22]=4[CH2:21][CH2:20]3)[CH:16]=[CH:17][CH:18]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.CCCP(=O)=O.[NH2:45][CH2:46][CH2:47][CH2:48][OH:49]>CN(C1C=CN=CC=1)C.ClCCCl>[OH:49][CH2:48][CH2:47][CH2:46][NH:45][C:29]([C:23]1[C:22]2[CH2:21][CH2:20][N:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([C:11]([NH:10][C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=4)=[O:12])[CH:14]=3)[CH2:28][C:27]=2[CH:26]=[N:25][CH:24]=1)=[O:30]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 90863-Amino-1-propanolHCID 16167369Propylphosphoric anhydrideHCID 717365027-(3-{[(3-Isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylic acid

Product 1

HCID 71736345N-(3-hydroxypropyl)-7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxamideYield 37.5%

Reagents, catalysts & solvents 2

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

Procedure

To a mixture of 7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylic acid (47 mg, 0.113 mmol), triethylamine (0.047 mL, 0.34 mmol), and catalytic DMAP in 3.0 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.081 mL, 0.136 mmol). After 5 min at rt, 3-amino-1-propanol (0.011 mL, 0.147 mmol) was added and the reaction stirred at rt for 2 hours. The reaction was quenched with aqueous NaHCO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, aqueous NaHCO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. This material was chromatographed eluting with CHCl3/EtOAc plus 10% MeOH to give the title compound as a light yellow solid (20 mg, 37%). 1H NMR (CDCl3) δ: 8.46 (s, 1H), 8.41 (s, 1H), 8.02 (s, 1H), 7.54 (s, 1H), 7.44-7.51 (m, 2H), 7.19-7.39 (m, 4H), 7.10 (d, J=8.2 Hz, 1H), 7.03 (d, J=7.6 Hz, 1H), 6.81 (t, J=5.6 Hz, 1H), 4.45 (s, 2H), 3.78 (t, J=5.4 Hz, 2H), 3.53-3.65 (m, 4H), 3.17 (t, J=5.6 Hz, 2H), 2.86-2.97 (m, 1H), 1.77-1.86 (m, 2H), 1.27 (d, J=6.7 Hz, 6H)

Workup

  1. customThe reaction was quenched with aqueous NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washthe EtOAc layer washed with H2O, aqueous NaHCO3 solution, brine
  4. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  5. customThis material was chromatographed
  6. washeluting with CHCl3/EtOAc plus 10% MeOH

Sources & evidence

ORD record
ord-d5ad504470524c9d87c43e7d339cfdfc
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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