Trifluoroacetic acid → 4-(3-(6-Chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361278ノート

反応式

HRID 2361278 の反応式
[C:1]([C:4]1[C:9]2[NH:10][C:11]3[C:16]([C:8]=2[C:7]([C:22]2[C:23]([CH3:40])=[C:24]([NH:28][CH2:29][C:30]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:31]=4[C:32]([OH:34])=O)[CH:25]=[CH:26][CH:27]=2)=[CH:6][N:5]=1)=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][O:20][CH3:21])[CH:12]=3)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O.C(NC(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[Cl:39][C:36]1[CH:35]=[C:31]2[C:30]([CH2:29][N:28]([C:24]3[C:23]([CH3:40])=[C:22]([C:7]4[C:8]5[C:16]6[C:11](=[CH:12][C:13]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:14][CH:15]=6)[NH:10][C:9]=5[C:4]([C:1]([NH2:2])=[O:3])=[N:5][CH:6]=4)[CH:27]=[CH:26][CH:25]=3)[C:32]2=[O:34])=[CH:38][CH:37]=1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 7912DiisopropylamineHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 679950002-((3-(1-Carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid

生成物 1

HCID 547517474-(3-(6-Chloro-1-oxoisoindolin-2-yl)-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide収率 68.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
45 °C

実験手順

A mixture of 2-((3-(1-carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid, TFA (38 mg, 0.056 mmol), N,N-diisopropylamine (0.015 mL, 0.085 mmol), BOP (32.5 mg, 0.073 mmol), and N-methylmorpholine (0.024 mL, 0.220 mmol) in DMF (4 mL) was heated at 45° C. for 1 hr. The mixture was diluted with ethyl acetate (60 mL), washed sequentially with water (3×25 mL) and brine (25 mL), and dried over anhydrous MgSO4. After the solvent was removed under vacuum, the residue was purified by prep. Reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with CH2Cl2 (3×30 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (21.7 mg, 0.039 mmol, 68.2% yield) as a yellow solid. LCMS (M+H)+=541.33. 1H NMR (500 MHz, DMSO-d6) δ: 11.66 (s, 1H), 8.30 (s, 1H), 8.20 (s, 1H), 7.82 (s, 1H), 7.77-7.73 (m, 3H), 7.67 (m, 1H), 7.54 (m, 1H), 7.45 (m, 1H), 7.36 (d, J=2.2 Hz, 1H), 7.14 (d, J=8.9 Hz, 1H), 6.71 (dd, J1=8.7 Hz, J2=2.4 Hz, 1H), 5.04 (d, J=17.5 Hz, 1H), 4.95 (d, J=17.5 Hz, 1H), 4.16 (m, 2H), 3.72 (m, 2H), 3.34 (s, 3H), 1.87 (s, 3H).

後処理

  1. washwashed sequentially with water (3×25 mL) and brine (25 mL)
  2. dry with materialdried over anhydrous MgSO4
  3. customAfter the solvent was removed under vacuum
  4. customthe residue was purified by prep
  5. concentrationThe correct fraction was concentrated under vacuum
  6. extractionextracted with CH2Cl2 (3×30 mL)
  7. extractionThe combined extract
  8. washwas washed with brine (30 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. customRemoval of solvent under vacuum

出典と根拠

ORDレコード
ord-96503e46c6e44e1383949ba99aca22f2
出典データセット
uspto-grants-2014_04
特許番号
US08685969B2

反応ノート

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