Oxalyl chloride → (1-(4-[(7-chloro-3-methylbenzofuran-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester

HRID 409400

反応式

HRID 409400 の反応式
[Cl:1][C:2]1[C:10]2[O:9][C:8]([C:11]([OH:13])=O)=[C:7]([CH3:14])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[C:21]([O:25][C:26](=[O:43])[CH2:27][C:28]1[C:29]([CH3:42])=[N:30][N:31]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=2)[C:32]=1[CH3:33])([CH3:24])([CH3:23])[CH3:22].C1(C)C(S([O-])(=O)=O)=CC=CC=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C1C=CN=CC=1.CN(C)C=O>[C:21]([O:25][C:26](=[O:43])[CH2:27][C:28]1[C:29]([CH3:42])=[N:30][N:31]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:11]([C:8]3[O:9][C:10]4[C:2]([Cl:1])=[CH:3][CH:4]=[CH:5][C:6]=4[C:7]=3[CH3:14])=[O:13])=[CH:39][CH:40]=2)[C:32]=1[CH3:33])([CH3:24])([CH3:23])[CH3:22]

参加物

9

反応物 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 23056317-chloro-3-methyl-benzofuran-2-carboxylic AcidHCID 3424274ToluenesulfonateHCID 67359516[1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid tert-butyl ester

生成物 1

HCID 68276364(1-(4-[(7-chloro-3-methylbenzofuran-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester収率 95.3%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 7-chloro-3-methylbenzofuran-2-carboxylic acid (185 mg, 0.88 mmol) in 6 mL dichloromethane is added oxalyl chloride (0.123 mL, 1.14 mmol) and a drop of dimethylformamide. After stirring at room temperature for 1 hour the solvent is removed by evaporation in vacuo. The residue is dissolved in dichloromethane (5 mL) and dropped to a solution of [1-(4-aminobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid tert-butyl ester (428 mg, 1 mmol) in form of the toluene sulfonate salt and diisopropylethylamine (0.39 mL, 2.27 mmol) in dichloromethane (5 mL). After addition of 4-dimethylaminopyridine (11 mg, 0.09 mmol) the solution is stirred at room temperature for 12 hours. The solution is extracted twice with hydrochloric acid (1 M), twice with water, twice with an aqueous solution of NaOH (1 M) and twice with water. The organic layer is dried over MgSO4, filtered and the solvent is evaporated in vacuo to yield 426 mg of (1-(4-[(7-chloro-3-methyl-benzofuran-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester (ESI mass spectrum: [M+H]+=508; Retention time HPLC: 1.60 min (method H)). b) To a solution of (1-(4-[(7-chloro-3-methyl-benzofuran-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid tert-butyl ester (426 mg, 0.84 mmol) in dichloromethane (10 mL) is added trifluoroacetic acid (400 mL, 5.2 mmol) and the mixture is stirred at room temperature for 3 days. The solvent is evaporated in vacuo, and the residue is suspended in water and treated with diethyl ether and the precipitating product is filtered off to yield 174 mg of the title compound (ESI mass spectrum: [M+H]+=452; Retention time HPLC: 1.39 min (method J)).

後処理

  1. customis removed by evaporation in vacuo
  2. dissolutionThe residue is dissolved in dichloromethane (5 mL)
  3. stirringis stirred at room temperature for 12 hours
  4. extractionThe solution is extracted twice with hydrochloric acid (1 M), twice with water, twice with an aqueous solution of NaOH (1 M) and twice with water
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. customthe solvent is evaporated in vacuo

出典と根拠

ORDレコード
ord-b307b041364a45afa6464fea272ab930
出典データセット
uspto-grants-2014_06
特許番号
US08759386B2

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