Triethylamine → 2-[1-[(3,5-dichloro-1H-pyrazol-1-yl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide

HRID 2043741ノート

反応式

HRID 2043741 の反応式
[Cl:1][C:2]1[CH:6]=[C:5]([Cl:7])[N:4]([CH2:8][C:9]([OH:11])=O)[N:3]=1.C(Cl)(=O)C(Cl)=O.Cl.[CH3:19][N:20]([C@H:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37][CH2:36][CH2:35]1)[C:21]([C:23]1[N:24]=[C:25]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[S:26][CH:27]=1)=[O:22].C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:6]=[C:5]([Cl:7])[N:4]([CH2:8][C:9]([N:31]2[CH2:32][CH2:33][CH:28]([C:25]3[S:26][CH:27]=[C:23]([C:21]([N:20]([CH3:19])[C@H:34]4[C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[CH2:37][CH2:36][CH2:35]4)=[O:22])[N:24]=3)[CH2:29][CH2:30]2)=[O:11])[N:3]=1

参加物

8

反応物 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 67460000HCID 67460000、化合物2 回HCID 67463124N-methyl-2-(4-piperidinyl)-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide monohydrochloride2 回

生成物 1

HCID 667962142-[1-[(3,5-dichloro-1H-pyrazol-1-yl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒3 回

実験手順

A solution of 3,5-dichloro-1H-pyrazol-1-acetic acid (70 mg, 0.36 mmol) (i.e. the product of Example 12, Step F) in dichloromethane (1 mL) and a catalytic amount of N,N-dimethylformamide (1 drop) was treated with oxalyl chloride (0.1 mL, 1.1 mmol) and stirred at ambient temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure and re-dissolved in dichloromethane (1 mL). The reaction mixture was added to a stirred suspension of N-methyl-2-(4-piperidinyl)-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide monohydrochloride (i.e. the product of Example 6, Step C) (100 mg, 0.26 mmol), triethylamine (0.1 mL, 0.72 mmol), and potassium carbonate (150 mg, 1 mmol) in dichloromethane (2 mL). The reaction mixture was then heated to reflux for 2 h, and then cooled to ambient temperature. The resulting suspension was diluted with dichloromethane (10 mL), filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography using 50-100% ethyl acetate in hexanes as eluant to give 80 mg of the title product, a compound of the present invention as an oil.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionre-dissolved in dichloromethane (1 mL)
  3. temperatureThe reaction mixture was then heated
  4. temperatureto reflux for 2 h
  5. temperaturecooled to ambient temperature
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-6fd65119812a41d4b6621d681a516791
出典データセット
uspto-grants-2013_11
特許番号
US08586611B2

反応ノート

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