Sodium Carbonate → Tert-butyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 596102노트

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HRID 596102 반응식
[NH2:1][C:2]1[C:7]([C:8]2[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[C:10]([F:21])[CH:9]=2)=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[O:37]=[C:38]1[CH:42]=[C:41](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:40][N:39]1[C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:41]2[CH2:40][N:39]([C:54]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:55])[C:38](=[O:37])[CH:42]=2)=[CH:6][C:7]=1[C:8]1[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[C:10]([F:21])[CH:9]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 10948184tert-butyl 2-oxo-4-(tosyloxy)-2,5-dihydro-1H-pyrrole-1-carboxylateHCID 123291347Tert-butyl 4-(2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2-fluorobenzoate

생성물 1

HCID 118045974Tert-butyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate수율 66%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
90 °C

실험 절차

To tert-butyl 4-(2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2-fluorobenzoate (158 mg, 0.382 mmol) in DME (3 mL) and sodium carbonate (0.509 mL, 1.019 mmol) was added tert-butyl 2-oxo-4-(tosyloxy)-2,5-dihydro-1H-pyrrole-1-carboxylate (90 mg, 0.255 mmol) and PdCl2(dppf)-CH2Cl2 (41.6 mg, 0.051 mmol). The reaction mixture was heated in microwave at 90° C. for 30 min. LCMS showed starting material remained. More catalysts were added and heated again at 90° C. for 20 min. The reaction mixture was partitioned between ethylacetate and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography using 0-50% EtOAc (contains 10% MeOH)/heptane to provide product as a yellow solid (66%). LCMS (m/z): 470.2 (MH+), 0.846 min.

후처리

  1. additionMore catalysts were added
  2. temperatureheated again at 90° C. for 20 min
  3. customThe reaction mixture was partitioned between ethylacetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-fcd1df023a434ea0923ee6cd89eaacab
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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