Diisopropylethylamine → (1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 1965172노트

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HRID 1965172 반응식
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([N:35]([CH3:41])[C@H:36]([C:38]([OH:40])=O)[CH3:37])([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].CCN(C(C)C)C(C)C.[NH2:51][CH:52]([C:78]([CH3:81])([CH3:80])[CH3:79])[C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:72]3[CH2:77][CH2:76][O:75][CH2:74][CH2:73]3)[CH2:61][CH:62]([O:63][C:64]3[CH:69]=[CH:68][C:67]([F:70])=[C:66]([F:71])[CH:65]=3)[CH:56]12)=[O:54]>CN1C(=O)CCC1>[CH2:28]([O:27][C:25](=[O:26])[N:35]([CH:36]([C:38](=[O:40])[NH:51][CH:52]([C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:72]3[CH2:77][CH2:76][O:75][CH2:74][CH2:73]3)[CH2:61][CH:62]([O:63][C:64]3[CH:69]=[CH:68][C:67]([F:70])=[C:66]([F:71])[CH:65]=3)[CH:56]12)=[O:54])[C:78]([CH3:80])([CH3:79])[CH3:81])[CH3:37])[CH3:41])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 7016365Z-N-Me-Ala-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 675142402-Amino-1-[6-(3,4-difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-one

생성물 1

HCID 67608273(1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester수율 81.2%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매2회

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온도
0 °C

실험 절차

HATU (126 mg, 0.33 mmol) and Cbz-N(Me)Ala-OH (79 mg, 0.33 mmol) were dissolved in NMP (0.5 mL) and DIPEA (70 μL, 0.39 mmol) was added. The reaction mixture was cooled to 0° C. and a solution of 26 (125 mg, 0.30 mmol) in NMP (2 mL) was added. The reaction mixture was warmed to ambient temperature. After 12 h, the reaction mixture was quenched with 1N NaOH (0.5 mL) and diluted with water. The product was extracted with 10:1 Et2O/EtOAc, and the combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 160 mg of 27 as a beige-colored foam that was used without further purification. Mass spectrum, m/z [657.2] (M+H)+.

후처리

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. customthe reaction mixture was quenched with 1N NaOH (0.5 mL)
  3. additiondiluted with water
  4. extractionThe product was extracted with 10:1 Et2O/EtOAc
  5. washthe combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5988792eb2bc43258dcb8cec36d2833b
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415486B2

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