Formaldehyde → N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-N'-(3-methylamino-5-trifluoromethyl-phenyl)-malonamide

HRID 2377538노트

반응식

HRID 2377538 반응식
C(OC(=O)[N:10]([CH2:20][C@H:21]([NH:27][C:28](=[O:44])[CH2:29][C:30](=[O:43])[NH:31][C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([NH2:42])[CH:33]=1)[C@@H:22]([OH:26])[CH2:23][CH2:24][CH3:25])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=1[CH3:19])C1C=CC=CC=1.C=O.[C:48](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:19][C:13]1[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:12]=1[CH2:11][NH:10][CH2:20][C@H:21]([NH:27][C:28](=[O:44])[CH2:29][C:30]([NH:31][C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([NH:42][CH3:48])[CH:33]=1)=[O:43])[C@@H:22]([OH:26])[CH2:23][CH2:24][CH3:25]

참가 물질

5

반응물 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68616642{(2S,3S)-2-[2-(3-amino-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxyhexyl}-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester

생성물 1

HCID 11306757N-{(1S,2S)-1-[(2,4-Dimethyl-benzylamino)-methyl]-2-hydroxy-pentyl}-N'-(3-methylamino-5-trifluoromethyl-phenyl)-malonamide

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

A solution of {(2S,3S)-2-[2-(3-amino-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxyhexyl}-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester (83 mg, 0.13 mmol, see procedure 12c) in 1,2-dichloroethane (2 mL) was charged with formaldehyde (0.008 mL of a 37% aq. solution, 0.10 mmol), stirred for 20 min at RT, and then charged with sodium triacetoxyborohydride (69 mg, 0.33 mmol). The reaction was stirred at RT for 40 min, quenched with water, and extracted with EtOAc (2×). The organic extracts were washed with water and brine, and then dried (Na2SO4), filtered, and concentrated in vacuo. The residue was dissolved in MeOH (2 mL). This solution was charged with 5% Pd/C, Degussa style (7 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. Purification of the residue by reverse-phase HPLC provided the title compound as a white powder after lyopholization. MS found: (M+H)+=509.3.

후처리

  1. stirringThe reaction was stirred at RT for 40 min
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in MeOH (2 mL)
  9. additionThis solution was charged with 5% Pd/C, Degussa style (7 mg)
  10. stirringstirred under H2 (1 atm) for 12 h at RT
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification of the residue by reverse-phase HPLC

출처 및 근거

ORD 기록
ord-15f607a7621c4351b746d9cf9775e90f
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07468440B2

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