Cesium carbonate → (S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate

HRID 596105노트

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HRID 596105 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.FC(F)(F)S(O[C:37]1[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:39]([C:49]([O:51][CH3:52])=[O:50])[CH:38]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:37]2[CH2:41][N:40]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C@H:39]([C:49]([O:51][CH3:52])=[O:50])[CH:38]=2)=[CH:6][C:7]=1[C:8]1[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])=[C:10]([F:21])[CH:9]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 11773246(S)-1-tert-Butyl 2-methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylateHCID 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 118045728(S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate수율 95%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
90 °C

실험 절차

A mixture of tert-butyl 4-(2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2-fluorobenzoate (400 mg, 0.966 mmol), (S)-1-tert-butyl 2-methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (1.087 g, 2.90 mmol, Pd(PPh3)4 (112 mg, 0.097 mmol) and cesium carbonate (1.258 g, 3.86 mmol) in THF (10 mL) and water (2 mL) was degassed, then microwave heated to 90° C. for 10 min. At completion, the reaction was diluted with ethyl acetate. The organics were washed with brine, dried over magnesium sulfate and concentrated. The crude mixture was purified by flash chromatography over silica gel (20-90% ethyl acetate/heptane) to provide (S)-1-tert-butyl 2-methyl 4-(6-amino-5-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyridin-3-yl)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (470 mg, 95%). LCMS (m/z): 514.3 (MH+), 0.92 min.

후처리

  1. customwas degassed
  2. additionAt completion, the reaction was diluted with ethyl acetate
  3. washThe organics were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude mixture was purified by flash chromatography over silica gel (20-90% ethyl acetate/heptane)

출처 및 근거

ORD 기록
ord-80f11a54d53e4ba298187e8dfbfa7776
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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