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4-Methylmorpholine → 4-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3,3-dimethyl-butyryl}-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965179
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HRID 1965179 반응식
[C:1]([N:11]([CH3:17])[C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:49]([O:53][C:54]([N:56]1[CH2:60][CH:59]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[C:64]([F:69])[CH:63]=2)[CH:58]2[N:70]([C:73](=[O:80])[CH:74]([NH2:79])[C:75]([CH3:78])([CH3:77])[CH3:76])[CH2:71][CH2:72][CH:57]12)=[O:55])([CH3:52])([CH3:51])[CH3:50]>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:49]([O:53][C:54]([N:56]1[CH2:60][CH:59]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[C:64]([F:69])[CH:63]=2)[CH:58]2[N:70]([C:73](=[O:80])[CH:74]([NH:79][C:14](=[O:16])[CH:12]([N:11]([C:1]([O:3][CH2:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)=[O:2])[CH3:17])[CH3:13])[C:75]([CH3:78])([CH3:77])[CH3:76])[CH2:71][CH2:72][CH:57]12)=[O:55])([CH3:52])([CH3:50])[CH3:51]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 79724-MethylmorpholineHCID 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 675179964-(2-Amino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

생성물 1

HCID 67606509
4-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3,3-dimethyl-butyryl}-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester
수율 89.2%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매2회

실험 절차

To a solution Cbz-N(Me)-Ala-OH (1.2 g, 4.8 mmol) and HATU (2.0 g, 5.3 mmol) in NMP (30 mL) was added NMM (0.7 mL) followed by a solution of compound 33 (1.8 g, 4.0 mmol crude) in NMP (30 mL) at ambient temperature. After 16 h, the reaction mixture was diluted with 10% EtOAc in Et2O, washed successively with water, 1N HCl, 1N NaOH, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue was purified by RP-HPLC (2″ Dynamax® C18; 10-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 2.4 g of compound 34 as white solid. Mass spectrum, m/z [673.0] (M+H)+.

후처리

  1. washwashed successively with water, 1N HCl, 1N NaOH, and brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by RP-HPLC (2″ Dynamax® C18
  6. wait10-100% ACN/water containing 0.1% HOAc over 30 min

출처 및 근거

ORD 기록
ord-4c3a30ed854548abb8fc709b39d002ea
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08415486B2

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