Dimethylformamide → 3-(3-aminoisoquinolin-7-yl)-N-cyclobutyl-4-methylbenzamide

HRID 1502431

反応式

HRID 1502431 の反応式
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15](O)=[O:16])[CH:6]=2.[CH:22]1([NH2:26])[CH2:25][CH2:24][CH2:23]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:15]([NH:26][CH:22]1[CH2:25][CH2:24][CH2:23]1)=[O:16])[CH:6]=2

参加物

8

反応物 5

HCID 6228DimethylformamideHCID 75645CyclobutylamineHCID 81531DiisopropylethylamineHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 679748773-(3-Aminoisoquinolin-7-yl)-4-methylbenzoic acid

生成物 1

HCID 679747473-(3-aminoisoquinolin-7-yl)-N-cyclobutyl-4-methylbenzamide収率 8.2%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 3-(3-aminoisoquinolin-7-yl)-4-methylbenzoic acid (43.0 mg; 0.155 mmol), cyclobutylamine (27 μL; 0.310 mmol), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (129.5 mg; 0.2384 mmol), N,N-diisopropylethylamine (0.1 mL; 0.6 mmol), 4-(dimethylamino)pyridine (0.1 equiv.; 0.0155 mmol) and N,N-dimethylformamide (2.0 mL; 26 mmol) was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with water (2×) and brine, dried over magnesium sulfate, and filtered through a plug of silica gel, rinsing with additional ethyl acetate. The filtrate was evaporated in vacuo to yield 53.6 mg crude product. 20.2 mg of crude product was purified via preparatory reverse-phase HPLC and lyophilized to yield 4.2 mg of the title compound. LCMS (ESI): RT (Min)=2.88, M+H=327.3, method=H; 1H NMR (400 MHz, DMSO) δ 8.87 (s, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.82-7.74 (m, 3H), 7.60 (d, J=8.6 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 6.67 (s, 1H), 5.95 (s, 2H), 4.50-4.34 (m, 1H), 2.31 (s, 3H), 2.26-2.13 (m, 2H), 2.06 (m, 2H), 1.73-1.57 (m, 2H).

後処理

  1. washwashed with water (2×) and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered through a plug of silica gel
  4. washrinsing with additional ethyl acetate
  5. customThe filtrate was evaporated in vacuo
  6. customto yield 53.6 mg crude product
  7. custom20.2 mg of crude product was purified via preparatory reverse-phase HPLC

出典と根拠

ORDレコード
ord-18a02fc01f2c4061b2f724b2923170c7
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

関連ノート

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