2,6-Dichlorobenzoyl chloride → 5-Amino-N-(2-{[[(2,6-dichlorophenyl)carbonyl](methyl)amino]methyl}-3,3,3-trifluoro-2-hydroxypropyl)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886718ノート

反応式

HRID 886718 の反応式
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([OH:26])([CH2:23][NH:24][CH3:25])[C:19]([F:22])([F:21])[F:20])=[O:15].C(N(C(C)C)CC)(C)C.[Cl:36][C:37]1[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:38]=1[C:39](Cl)=[O:40]>O1CCCC1>[C:18]([O-:26])(=[O:40])[CH3:23].[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:23][N:24]([C:39]([C:38]1[C:37]([Cl:36])=[CH:45][CH:44]=[CH:43][C:42]=1[Cl:46])=[O:40])[CH3:25])([OH:26])[C:19]([F:22])([F:21])[F:20])=[O:15]

参加物

6

反応物 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 594874925-Amino-1-(4-fluorophenyl)-N-{3,3,3-trifluoro-2-hydroxy-2-[(methylamino)methyl]propyl}-1H-pyrazole-4-carboxamide

生成物 2

HCID 175AcetateHCID 594875115-Amino-N-(2-{[[(2,6-dichlorophenyl)carbonyl](methyl)amino]methyl}-3,3,3-trifluoro-2-hydroxypropyl)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide収率 135.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 5-amino-1-(4-fluorophenyl)-N-{3,3,3-trifluoro-2-hydroxy-2-[(methylamino)methyl]propyl}-1H-pyrazole-4-carboxamide (56 mg, 0.15 mmol) in anhydrous tetrahydrofuran (2 ml) cooled in ice was added diisopropylethylamine (0.052 ml, 0.3 mmol) followed by 2,6-dichlorobenzoyl chloride (0.023 ml, 0.164 mmol). After 20 minutes, the mixture was removed from the ice and left at 21° C. for 19 hours. The mixture was blown down, the residue was dissolved in dichloromethane (3 ml) and washed with 2M hydrochloric acid (1 ml) and water (1 ml). It was again blown down and purified on a 5 g SPE cartridge, eluting with dichloromethane and then mixtures of cyclohexane/ethyl:acetate (10:1), (5:1), (3:1) and finally (2:1) to give the title compound (55.6 mg).

後処理

  1. customthe mixture was removed from the ice
  2. waitleft at 21° C. for 19 hours
  3. dissolutionthe residue was dissolved in dichloromethane (3 ml)
  4. washwashed with 2M hydrochloric acid (1 ml) and water (1 ml)
  5. custompurified on a 5 g SPE cartridge
  6. washeluting with dichloromethane

出典と根拠

ORDレコード
ord-409c5855d36b4265bc02e23118123bea
出典データセット
uspto-grants-2012_08
特許番号
US08247377B2

反応ノート

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