Dimethylformamide → tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526390노트

반응식

HRID 526390 반응식
[C:1]([O:5][C:6](=[O:50])[CH2:7][C@H:8]([NH:24][C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)[CH2:28]1)=[O:26])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:51](=[O:54])([O-])[O-].[Cs+].[Cs+].[CH3:57][C:58]1[CH:63]=[CH:62][C:61]([S:64]([O-:67])(=O)=[O:65])=[CH:60][CH:59]=1.[CH3:68]N(C)C=O>>[C:1]([O:5][C:6](=[O:50])[CH2:7][C@H:8]([NH:24][C:25]([C@@H:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33](=[O:49])[CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)[CH2:28]1)=[O:26])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:68][CH2:51][O:54][S:64]([C:61]3[CH:62]=[CH:63][C:58]([CH3:57])=[CH:59][CH:60]=3)(=[O:67])=[O:65])[CH:18]=2)[CH:14]=1)([CH3:3])([CH3:2])[CH3:4]

참가 물질

5

반응물 4

HCID 6228DimethylformamideHCID 10796Cesium carbonate2회HCID 85570p-Toluenesulfonate2회HCID 71609226tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 89407548tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

실험 절차

Tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[(3-hydroxyphenyl)ethynyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (40 mg, 0.06 mmol) was dissolved in N,N-dimethylformamide (6.7 mL). Cesium carbonate (47 mg, 0.15 mmol) and ethane-1,2-diyl bis(4-methylbenzenesulfonate (32 mg, 0.09 mmol) were added. The mixture was stirred at room temperature for 4 hours and stored for 72 hours at 5° C. The addition of cesium carbonate (47 mg, 0.15 mmol) and ethane-1,2-diyl bis(4-methylbenzenesulfonate (32 mg, 0.09 mmol) was repeated and the mixture was stirred at room temperature for 3 hours. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 50%) to yield 24 mg of tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-{[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]ethynyl}pyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

후처리

  1. waitstored for 72 hours at 5° C
  2. stirringthe mixture was stirred at room temperature for 3 hours
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  4. extractionextracted with ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 50%)

출처 및 근거

ORD 기록
ord-1fa1ec7aa95347b0a58f7c8cb77b1a8d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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