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

HRID 541401노트

반응식

HRID 541401 반응식
[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]

참가 물질

9

반응물 5

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 682882755-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzoic acid2회

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 21584119Ethylacetate methanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-de43bbd53b7742beb07d79e132eea57b
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871790B2

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