tert-Butyl piperazine-1-carboxylate → N-(3-tert-Butyl-phenyl)-3-fluoro-4-piperazin-1-yl-benzamide

HRID 2190547노트

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HRID 2190547 반응식
Br[C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:10]=2)=[O:7])=[CH:4][C:3]=1[F:21].C(OC([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=O)(C)(C)C.CC([O-])(C)C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[C:15]([C:11]1[CH:10]=[C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:19]=[CH:20][C:2]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[C:3]([F:21])[CH:4]=2)[CH:14]=[CH:13][CH:12]=1)([CH3:18])([CH3:17])[CH3:16]

참가 물질

6

반응물 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 593181654-Bromo-N-(3-tert-butyl-phenyl)-3-fluoro-benzamide

생성물 1

HCID 59318037N-(3-tert-Butyl-phenyl)-3-fluoro-4-piperazin-1-yl-benzamide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
85 °C

실험 절차

The 4-bromo-N-(3-tert-butyl-phenyl)-3-fluoro-benzamide (0.15 mmol) was added piperazine-1-carboxylic acid tert-butyl ester (0.195 mmol), NaOtBu (0.375 mmol), XantPhos (0.03 mmol), Pd2 dba2 (0.009 mmol) and 1,4 dioxane (0.2 mL). The reaction vial was purged with Ar, sealed, and heated at 85° C. overnight. The reaction was worked up by diluting with ethyl acetate (mL) washed with NH4Cl (1.5 M, 4 mL), and brine (4 mL), filtered through a plug of Na2SO4, and dried under a stream of nitrogen. To the intermediate was added DCM (1 ml) and TFA (0.2 mL) and stirred at room temperature for 1 hr. The reaction was diluted ethyl acetate (mL) washed with NaHCO3 (saturated, 4 mL, twice), and brine (4 mL), filtered through a plug of Na2SO4 and dried under a stream of nitrogen yielding the product, N-(3-tert-butyl-phenyl)-3-fluoro-4-piperazin-1-yl-benzamide. LCMS calcd for C21H26FN3O (m/e) 355, obsd 356 (M+H).

후처리

  1. customThe reaction
  2. customvial was purged with Ar
  3. customsealed
  4. additionby diluting with ethyl acetate (mL)
  5. washwashed with NH4Cl (1.5 M, 4 mL), and brine (4 mL)
  6. filtrationfiltered through a plug of Na2SO4
  7. customdried under a stream of nitrogen
  8. additionTo the intermediate was added DCM (1 ml) and TFA (0.2 mL)
  9. washwashed with NaHCO3 (saturated, 4 mL
  10. filtrationtwice), and brine (4 mL), filtered through a plug of Na2SO4
  11. dry with materialdried under a stream of nitrogen yielding the product, N-(3-tert-butyl-phenyl)-3-fluoro-4-piperazin-1-yl-benzamide

출처 및 근거

ORD 기록
ord-c796eee6f05641e6ab92bd3e8de06a67
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324385B2

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