Acetic Acid → N-[1-(cyclobutylmethyl)-3-methylpyrrolidin-3-yl]-N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]cyclohexanecarboxamide

HRID 1943032

反応式

HRID 1943032 の反応式
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH2:12][N:13]([C:22]2([CH3:27])[CH2:26][CH2:25][NH:24][CH2:23]2)[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[C:3]1=[O:28].[CH:29]1([CH:33]=O)[CH2:32][CH2:31][CH2:30]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH:29]1([CH2:33][N:24]2[CH2:25][CH2:26][C:22]([N:13]([CH2:12][C:4]3[C:3](=[O:28])[N:2]([CH3:1])[C:11]4[C:6]([CH:5]=3)=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:14]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])([CH3:27])[CH2:23]2)[CH2:32][CH2:31][CH2:30]1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 12431621CyclobutanecarbaldehydeHCID 58415934N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-(3-methylpyrrolidin-3-yl)cyclohexanecarboxamide

生成物 1

HCID 58415936N-[1-(cyclobutylmethyl)-3-methylpyrrolidin-3-yl]-N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]cyclohexanecarboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-(3-methylpyrrolidin-3-yl)cyclohexanecarboxamide (300 mg, 0.786 mmol), cyclobutanecarbaldehyde (99 mg, 1.180 mmol), and acetic acid (0.090 ml, 1.573 mmol) were combined in CH2Cl2 (70 ml). Sodium triacetoxyborohydride (333 mg, 1.573 mmol) was added and the reaction stirred for 2.5 hours. The reaction mixture was partitioned between CH2Cl2 and satd. bicarb, the aqueous portion extracted 3×CH2Cl2, and the organic portion dried (Na2SO4) then concentrated in vacuo. The resulting material was purified in two batches by reversed phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 50 ml/min, 30×100 mm Phenomenex Gemini C18 column). Desired fractions were combined and concentrated in vacuo. HRMS [M+H]1+ 450.3099. 1H NMR (400 MHz, CDCl3): δ 7.62-7.55 (m, 3 H); 7.42 (d, J=8.5 Hz, 1 H); 7.29 (t, J=7.6 Hz, 1 H); 4.44 (s, 2 H); 3.80 (s, 3 H); 2.99 (d, J=10.0 Hz, 1 H); 2.85 (d, J=10.2 Hz, 1 H); 2.53 (t, J=7.9 Hz, 1 H); 2.47-2.35 (m, 4 H); 2.09-1.92 (m, 5 H); 1.92-1.64 (m, 14 H); 1.28-0.99 (m, 3 H). 210 mg, 59%.

後処理

  1. customThe reaction mixture was partitioned between CH2Cl2 and satd
  2. extractionbicarb, the aqueous portion extracted 3×CH2Cl2
  3. dry with materialthe organic portion dried (Na2SO4)
  4. concentrationthen concentrated in vacuo
  5. customThe resulting material was purified in two batches by reversed phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 50 ml/min, 30×100 mm Phenomenex Gemini C18 column)
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-157e1be0a62845438cdf1b9761bcccfe
出典データセット
uspto-grants-2013_03
特許番号
US08389720B2

関連ノート

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