Potassium Phosphate, Tribasic → (2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate

HRID 1177533노트

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HRID 1177533 반응식
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[CH:12][C:11]=1[C:25]1[S:26][C:27]2[C:32]([N:33]=1)=[CH:31][CH:30]=[C:29]([C:34]1([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:36][CH2:35]1)[N:28]=2.FC(F)(F)S(O[C:49]1[CH2:53][N:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:51]([C:61]([O:63][CH3:64])=[O:62])[CH:50]=1)(=O)=O>CN(C=O)C>[F:9][C:10]1[CH:15]=[C:14]([C:49]2[CH2:53][N:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:51]([C:61]([O:63][CH3:64])=[O:62])[CH:50]=2)[CH:13]=[CH:12][C:11]=1[C:25]1[S:26][C:27]2[C:32]([N:33]=1)=[CH:31][CH:30]=[C:29]([C:34]1([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:35][CH2:36]1)[N:28]=2

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 11773246(S)-1-tert-Butyl 2-methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylateHCID 671119352-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

생성물 1

HCID 67112968(2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A slurry of potassium phosphate (2.50 g, 11.8 mmol), (Amphos)2PdCl2 (0.125 g, 0.177 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (2.78 g, 5.89 mmol) and (S)-1-tert-butyl 2-methyl 4-(trifluoromethylsulfonyloxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (2.21 g, 5.89 mmol, synthesized according to literature reference: Bioorganic and Medicinal Chemistry Letters, 2007, 2715) in 15 mL DMF was flushed with argon, sealed, and heated to 80° C. After 6 h, the reaction was judged complete, cooled, and filtered through celite, rinsing with 200 mL EtOAc. The filtrate was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel chromatography, EA/hexanes gradient, gave (2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate as a light yellow solid. MS (ESI) m/z: Calculated: 571.2; Observed: 572.1 (M++1).

후처리

  1. customsealed
  2. temperaturecooled
  3. filtrationfiltered through celite
  4. washrinsing with 200 mL EtOAc
  5. washThe filtrate was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography, EA/hexanes gradient

출처 및 근거

ORD 기록
ord-0ac67b9abfa9416a91daef1e78fe467a
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842685B2

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