Hydrogen Bromide → Tenofovir

HRID 554464

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HRID 554464 반응식
C([C:3](CC)([P:18]([OH:21])([OH:20])=[O:19])[O:4][C@H:5]([CH3:17])[CH2:6][N:7]1[CH:15]=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][C:12]=2[NH2:16])C.Br>C(O)(=O)C.Cl.CC(O)C>[P:18]([CH2:3][O:4][C@H:5]([CH3:17])[CH2:6][N:7]1[CH:15]=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][C:12]=2[NH2:16])([OH:20])([OH:21])=[O:19]

참가 물질

6

반응물 2

HCID 260Hydrogen Bromide2회HCID 67460257(R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine2회

생성물 1

HCID 464205Tenofovir

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 313Hydrochloric Acid용매2회HCID 3776Isopropanol용매

반응 조건

온도
92.5 °C

실험 절차

Dealkylation of (R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine is carried out in presence of a suitable dealkylating reagents selected from mineral acids like aq. HBr, aq. HCl, HBr in acetic acid or HCl gas in IPA with mole ratio ranging from 3 to 15 preferably 7.5 moles and typically at a temperature of about 25 to 110° C., usually at 90 to 95° C. (R)-9-[2-(Diethyl phosphonomethoxy)propyl]adenine and one of the acid described above are maintained at 90 to 95° C. for about 3 to 15 hrs, after completion of reaction, the reaction mass is washed with Methylenedichloride and pH is adjusted to about 1.5 to 3.5 preferably at 2.5 to 3.0 with caustic lye solution. Reaction mass is cooled to about 25 to 35° C. and finally to about 0 to 5° C. over 4 to 10 hrs. The precipitated product is filtered and the wet material is recrystallized in water to get pure (R)-9-[2-(phosphonomethoxy)propyl]adenine with improved yield.

후처리

  1. customranging from 3 to 15 preferably 7.5 moles and typically at a temperature of about 25 to 110° C., usually at 90 to 95° C.
  2. customafter completion of reaction
  3. washthe reaction mass is washed with Methylenedichloride and pH
  4. customReaction mass
  5. temperatureis cooled to about 25 to 35° C. and finally to about 0 to 5° C. over 4 to 10 hrs
  6. filtrationThe precipitated product is filtered
  7. customthe wet material is recrystallized in water

출처 및 근거

ORD 기록
ord-9dd785a1580b4faa80fdcfc77899ff12
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08049009B2

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