Carbonate Ion → N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3-fluoro-1-piperidyl)methyl]benzamide

HRID 16742

反応式

HRID 16742 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OC([N:18]1[C:22]([NH2:23])=[CH:21][C:20]([CH2:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=2)=[N:19]1)=O)(C)(C)C.[F:36][CH:37]1[CH2:42][CH2:41][CH2:40][N:39]([CH2:43][C:44]2[CH:53]=[CH:52][C:47]([C:48](OC)=[O:49])=[CH:46][CH:45]=2)[CH2:38]1.C(=O)([O-])[O-]>C1COCC1.CC#N>[CH3:33][O:32][C:30]1[CH:31]=[C:26]([CH2:25][CH2:24][C:20]2[NH:19][N:18]=[C:22]([NH:23][C:48](=[O:49])[C:47]3[CH:46]=[CH:45][C:44]([CH2:43][N:39]4[CH2:40][CH2:41][CH2:42][CH:37]([F:36])[CH2:38]4)=[CH:53][CH:52]=3)[CH:21]=2)[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1

参加物

7

反応物 4

HCID 19660Carbonate IonHCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440371Tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylateHCID 57440390Methyl 4-[(3-fluoro-1-piperidyl)methyl]benzoate

生成物 1

HCID 66589651N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-[(3-fluoro-1-piperidyl)methyl]benzamide収率 16%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of NaHMDS in THF (1 M, 0.86 ml, 0.86 mmol, 1.5 eq) was added dropwise at ambient temperature to a mixture of tert-butyl-5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]pyrazole-1-carboxylate (200 mg, 0.58 mmol, 1 eq) and methyl 4-[(3-fluoro-1-piperidyl)methyl]benzoate (174 mg, 0.69 mmol, 1.2 eq) in THF (1 ml). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was then concentrated and the crude product was purified by reverse-phase prep. HPLC (acidic) using a gradient of acetonitrile in water containing 0.1% TFA. The clean fractions were taken and evaporated. The residue was dissolved in 3:1 DCM:MeCN mixture (4 ml) and MP-carbonate (2.74 mmol/g, 1 g, 2.74 mmol) was added. The mixture was stirred for 4 h, filtered and the filtrate evaporated to afford the title compound as a pale yellow gum (43 mg, 16% yield); 1H NMR (399.902 MHz, DMSO) δ 1.46-1.34 (2H, m), 1.82-1.61 (2H, m), 2.36-2.28 (2H, m), 2.66-2.56 (2H, m), 2.81 (4H, s), 3.50 (2H, s), 3.65 (6H, s), 4.66-4.47 (1H, m), 6.26-6.24 (1H, m), 6.35 (2H, d), 6.40 (1H, s), 7.32 (2H, d), 7.88 (2H, d), 10.51 (1H, br.s), 12.07 (1H, br.s).

後処理

  1. concentrationThe reaction mixture was then concentrated
  2. customthe crude product was purified by reverse-phase prep
  3. customevaporated
  4. dissolutionThe residue was dissolved in 3:1 DCM
  5. stirringThe mixture was stirred for 4 h
  6. filtrationfiltered
  7. customthe filtrate evaporated

出典と根拠

ORDレコード
ord-03fd8373f0044890ad4fbfa6a75d9411
出典データセット
uspto-grants-2010_06
特許番号
US07737149B2

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