Methylamine → 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-N,4-dimethylbenzamide

HRID 541401ノート

反応式

HRID 541401 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH3:30])=[CH:19][C:20]([CH:26]4[CH2:29][CH2:28][CH2:27]4)=[C:21]([CH:25]=3)[C:22](O)=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C[CH2:32][N:33]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.CN>CN(C=O)C.C(OCC)(=O)C.CO.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[C:18]([CH3:30])=[CH:19][C:20]([CH:26]4[CH2:27][CH2:28][CH2:29]4)=[C:21]([CH:25]=3)[C:22]([NH:33][CH3:32])=[O:23])=[O:16])[CH2:13][CH2:14]2)=[CH:7][CH:8]=1)#[N:2]

参加物

9

反応物 5

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 682882755-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzoic acid2 回

生成物 1

HCID 665460165-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-N,4-dimethylbenzamide収率 55%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 21584119Ethylacetate methanol溶媒

実験手順

To a solution of 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzoic acid (compound 234, 50 mg, 0.124 mmol) in DMF (2 mL) were added EDCI (36 mg, 0.186 mmol), HOBt (10 mg, 0.5 mmol), diisopropylethyl amine (54 mg, 0.434 mmol), and methyl amine (125 ul, 2.5 M in THF). The reaction mixture was stirred for 12 hours at room temperature and quenched with saturated aqueous NaHCO3 (50 mL). After extraction with ethyl acetate (2×50 mL), the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification via SiO2 flash chromatography with ethyl acetate to ethyl acetate/methanol=98/2 afforded 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-N,4-dimethylbenzamide (28.3 mg, 55% yield) as a white solid. m/z (ES+) 416 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 8.13 (q, J=4.5 Hz, 1H), 7.77 (d, J=8.3 Hz, 2H), 7.55-7.45 (m, 2H), 7.26 (br s, 1H), 7.12 & 6.99 (2 singlets, amide rotamers, Ar—H, 1H), 4.70 (br d, J=11.9 Hz, 1H), 3.86-3.72 (m, 1H), 3.50-3.35 (m, 1H), 3.13 (t with fine structure, J=12.3 Hz, 1H), 2.99-2.78 (m, 2H), 2.72 (d, J=4.6 Hz, 3H), 2.39-2.17 (m, 5H), 2.17-1.98 (m, 2H), 1.98-1.81 (m, 2H), 1.81-1.35 (m, 4H).

後処理

  1. customquenched with saturated aqueous NaHCO3 (50 mL)
  2. extractionAfter extraction with ethyl acetate (2×50 mL)
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-de43bbd53b7742beb07d79e132eea57b
出典データセット
uspto-grants-2014_10
特許番号
US08871790B2

反応ノート

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