N-methyl-2-pyrrolidone → (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 1965176노트

반응식

HRID 1965176 반응식
CN(C(ON1N=NC2C=[CH:13][CH:14]=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]([C:72]3N=CC=CN=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].CN1[C:87](=[O:88])[CH2:86]CC1>>[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[CH2:14][CH2:13][O:88][CH2:87][CH2:86]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]([CH3:79])([CH3:81])[CH3:80])[CH3:37])[CH3:41])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

참가 물질

6

반응물 5

HCID 13387N-methyl-2-pyrrolidone2회HCID 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 675059372-Amino-1-[6-(3,4-difluoro-phenoxy)-4-pyrimidin-2-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 100%

반응 조건

온도
0 °C

실험 절차

HATU (105 mg, 0.28 mmol) and Cbz-N(Me)Ala-OH (65 mg, 0.28 mmol) were dissolved in NMP (0.5 mL) and DIPEA (65 μL, 0.36 mmol) was added. The reaction mixture was cooled to 0° C. and a solution of 30 (106 mg, 0.25 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, extracted with 10:1 Et2O/EtOAc. The combined organic extracts were washed successively with water, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 180 mg (100%) of 31 as a beige-colored foam which was used without further purification. Mass spectrum, m/z [651.2] (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. extractionextracted 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-714609eaa61e48d396685b9d73b94b63
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415486B2

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