Triethylamine → ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate

HRID 2376138노트

반응식

HRID 2376138 반응식
C(OP([CH:9]([F:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[Br-].[Mg+2].[Br-].CCN(CC)CC.[CH2:26]([N:33]1[CH2:37][CH2:36][C@@H:35]([NH:38][C:39]2[C:46]([Cl:47])=[CH:45][C:42]([CH:43]=O)=[CH:41][N:40]=2)[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1.C(OCC)(C)=O.O>[CH2:26]([N:33]1[CH2:37][CH2:36][C@@H:35]([NH:38][C:39]2[N:40]=[CH:41][C:42](/[CH:43]=[C:9](\[F:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:45][C:46]=2[Cl:47])[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 82241Magnesium BromideHCID 2734865Triethyl 2-fluoro-2-phosphonoacetateHCID 866037486-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde

생성물 1

HCID 86603747ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate수율 81.6%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 22728543Water ethylacetate용매

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온도
7.5 °C

실험 절차

To a mixture of ethyl (diethoxyphosphoryl)(fluoro)acetate (1.46 g) and magnesium bromide (1.33 g) in THF (20 ml) was added dropwise to a Et3N (0.92 ml) with stirring at 0-15° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at same condition for an hour. A solution of 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinaldehyde (1.36 g) in THF (10 ml) solution was added the above mixture and resultant mixture was stirred at 0-15° C. for 4 hours. The reaction mixture was poured into a mixture of AcOEt-H2O and the organic layer was washed with brine and dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-n-hexane (3:7). The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2Z)-3-(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridinyl)-2-fluoroacrylate (1.42 g).

후처리

  1. stirringthe reaction mixture was stirred at same condition for an hour
  2. stirringwas stirred at 0-15° C. for 4 hours
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was chromatographed on silicagel
  7. washeluting with AcOEt-n-hexane (3:7)
  8. additionThe eluted fractions containing the desired product
  9. customwere collected
  10. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-b9c2b3ff478e48b88254e7a7e2d311f1
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07465731B2

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