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tert-Butanol → N-[6-(1,4-dioxaspiro[4.5]decan-7-en-8-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamide

HRID 1748645
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HRID 1748645 반응식
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([NH2:19])=[O:18].Br[C:21]1[CH:22]=[C:23]([CH3:37])[C:24]([C:27]2[CH2:36][CH2:35][C:30]3([O:34][CH2:33][CH2:32][O:31]3)[CH2:29][CH:28]=2)=[N:25][CH:26]=1.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].C(O)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.O>[O:31]1[C:30]2([CH2:35][CH2:36][C:27]([C:24]3[N:25]=[CH:26][C:21]([NH:19][C:17]([C:3]4[CH:4]=[N:5][N:6]([C:7]5[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][CH:8]=5)[C:2]=4[CH3:1])=[O:18])=[CH:22][C:23]=3[CH3:37])=[CH:28][CH2:29]2)[O:34][CH2:33][CH2:32]1
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참가 물질

8

반응물 4

HCID 6386tert-ButanolHCID 24243Trisodium PhosphateHCID 178227615-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamideHCID 866924755-Bromo-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-3-methylpyridine

생성물 1

HCID 86692585N-[6-(1,4-dioxaspiro[4.5]decan-7-en-8-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamide
수율 85.9%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphane촉매HCID 962Water용매

반응 조건

온도
110 °C

실험 절차

A suspension of 5-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamide (538 mg), 5-bromo-2-(1,4-dioxaspiro[4.5]decan-7-en-8-yl)-3-methylpyridine (620 mg) described in Reference Example 105, tris(dibenzylideneacetone)dipalladium (0) (18 mg), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropylbiphenyl (48 mg), trisodium phosphate (509 mg) and tert-butanol (10 ml) was stirred at 110° C. After the reaction, the reaction solution was left stand, water was added and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with a silica gel column chromatography (chloroform/methanol) to give N-[6-(1,4-dioxaspiro[4.5]decan-7-en-8-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)-phenyl]-1H-pyrazole-4-carboxamide (856 mg) as a pale yellow solid.

후처리

  1. customAfter the reaction
  2. additionwas added
  3. extractionextracted with chloroform
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue was purified with a silica gel column chromatography (chloroform/methanol)

출처 및 근거

ORD 기록
ord-79d12d26ee9a457cbc45ca00d8db1063
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09150555B2

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