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

HRID 1052084ノート

反応式

HRID 1052084 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[N:13][CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][N:9]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18]([OH:20])=O)[CH2:10]2)=[O:4].C(N(CC)CC)C.CCCP(=O)=O.[CH:37]([C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43])([CH3:39])[CH3:38]>CN(C1C=CN=CC=1)C.ClCCCl>[CH:37]([C:40]1[CH:41]=[C:42]([NH:43][C:18]([C:17]2[CH:16]=[C:15]([N:9]3[CH2:10][C:11]4[CH:12]=[N:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[C:6]=4[CH2:7][CH2:8]3)[CH:23]=[CH:22][CH:21]=2)=[O:20])[CH:44]=[CH:45][CH:46]=1)([CH3:39])[CH3:38]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 4586793-IsopropylanilineHCID 16167369Propylphosphoric anhydrideHCID 866958813-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid

生成物 1

HCID 71736176Methyl 7-(3-{[(3-isopropylphenyl)amino]carbonyl}phenyl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carboxylate収率 68.7%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 111,2-Dichloroethane溶媒

実験手順

To a mixture of 3-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid (63 mg, 0.20 mmol), triethylamine (0.056 mL, 0.40 mmol), and catalytic DMAP in 2.0 mL 1,2-dichloroethane at rt was added propylphosphonic anhydride solution (50 wt % in EtOAc, 0.143 mL, 0.24 mmol). After 10 min at rt, 3-isopropylaniline (0.042 mL, 0.30 mmol) was added and the reaction stirred at rt for 1 hour. The reaction was quenched into aqueous NaHCO3 solution, extracted with EtOAc, the EtOAc layer washed with H2O, dilute aqueous NaHCO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. This material was chromatographed eluting with CHCl3/EtOAc to give the title compound as a light yellow solid (59 mg, 68%). 1H NMR (Acetone-d6) δ: 9.39 (br. s., 1H), 8.89 (s, 1H), 8.66 (s, 1H), 7.72-7.74 (m, 1H), 7.66-7.71 (m, 2H), 7.35-7.44 (m, 2H), 7.25-7.30 (m, 2H), 7.00 (d, J=7.6 Hz, 1H), 4.60 (s, 2H), 3.91 (s, 3H), 3.66-3.71 (m, 2H), 3.37 (t, J=5.9 Hz, 2H), 2.91 (spt, J=6.9 Hz, 1H), 1.25 (d, J=7.0 Hz, 6H)

後処理

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

出典と根拠

ORDレコード
ord-03ea9fc2849d4afb92075a496094c7d3
出典データセット
uspto-grants-2016_07
特許番号
US09388176B2

反応ノート

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