Dimethylformamide → (S)-4-(2'-amino-7-(cyclopropylethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

HRID 1970355노트

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HRID 1970355 반응식
FC(F)(S(O[C:17]1[CH:18]=[C:19]2[C@@:30]3([CH2:34][O:33][C:32]([NH2:35])=[N:31]3)[C:29]3[C:24](=[N:25][CH:26]=[C:27]([C:36]#[C:37][C:38]([OH:41])([CH3:40])[CH3:39])[CH:28]=3)[O:23][C:20]2=[CH:21][CH:22]=1)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.CN(C=O)C.C(NC(C)C)(C)C.[C:55]([CH:57]1[CH2:59][CH2:58]1)#[CH:56]>O.[Cu]I>[NH2:35][C:32]1[O:33][CH2:34][C@:30]2([C:29]3[C:24](=[N:25][CH:26]=[C:27]([C:36]#[C:37][C:38]([CH3:40])([OH:41])[CH3:39])[CH:28]=3)[O:23][C:20]3[C:19]2=[CH:18][C:17]([C:56]#[C:55][CH:57]2[CH2:59][CH2:58]2)=[CH:22][CH:21]=3)[N:31]=1

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 138823CyclopropylacetyleneHCID 86640731(S)-2'-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-7-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate

생성물 1

HCID 58466154(S)-4-(2'-amino-7-(cyclopropylethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazole]-3-yl)-2-methylbut-3-yn-2-ol

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매

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온도
80 °C

실험 절차

A 0.5-2 mL vial was charged with (S)-2′-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate (106 mg, 0.167 mmol), and copper(i) iodide (3.19 mg, 0.017 mmol). The vial was flushed with Ar (g), then DMF (669 μL, 0.167 mmol), diisopropylamine (469 μL, 3.35 mmol), and ethynylcyclopropane (70.8 μL, 0.836 mmol) were added in sequence to give a yellow solution. The vial was sealed and heated overnight in at 80° C. The mixture was diluted with water (15 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 40-g Redi-Sep column, eluting with 0-50% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM to give (S)-4-(2′-amino-7-(cyclopropylethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-3-yl)-2-methylbut-3-yn-2-ol as a tan solid after evaporation from DCM/hexanes.

후처리

  1. customThe vial was flushed with Ar (g)
  2. customto give a yellow solution
  3. customThe vial was sealed
  4. extractionextracted with EtOAc (3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography on a 40-g Redi-Sep column
  10. washeluting with 0-50% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM

출처 및 근거

ORD 기록
ord-395b4cebd5e645c887e626b900e020f8
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426447B2

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