Dicyclohexylamine → 4-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965168ノート

反応式

HRID 1965168 の反応式
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[C:3]([CH3:6])([CH3:5])[CH3:4].C1CCC(NC2CCCCC2)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[NH:85][CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:66])[CH3:65]>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[N:85]([C:7](=[O:9])[CH:2]([NH:1][C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[C:3]([CH3:4])([CH3:5])[CH3:6])[CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:65])[CH3:66]

参加物

9

反応物 5

HCID 7582DicyclohexylamineHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9899995(2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 676064563-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

生成物 1

HCID 676074394-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒2 回

実験手順

To a solution containing Cbz-Tle-OH.DCHA salt (4.1 g, 9.0 mmol) and HATU (3.8 g, 10 mmol) in NMP (50 mL) was added NMM (1.5 mL), followed by a solution of crude 22 (2.6 g, 7.5 mmol) in NMP (50 mL) at room temperature. The reaction mixture was stirred at room 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 3.5 g of 23 as white foam. Mass spectrum, m/z [688.3] (M+H)+.

後処理

  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

出典と根拠

ORDレコード
ord-33c5dd7a1f61474b9e8d7757c3a9f7a5
出典データセット
uspto-grants-2013_04
特許番号
US08415486B2

反応ノート

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