Hydrochloric Acid → Bortezomib

HRID 455964노트

반응식

HRID 455964 반응식
Cl.[N:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]([NH:10][C@H:11]([C:19]([OH:21])=O)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9].OC(C(O)(C)C)(C)C.[BH:30]([OH:32])[OH:31].[NH2:33][C@H:34](C(O)=O)[CH2:35][CH:36]([CH3:38])[CH3:37].CC(C)CB(O)O>CO.CCCCCCC>[B:30]([OH:32])([OH:31])[C@@H:34]([NH:33][C:19]([C@@H:11]([NH:10][C:8]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][N:2]=1)=[O:9])[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:21])[CH2:35][CH:36]([CH3:38])[CH3:37]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 2734395(2-Methylpropyl)boronic acidHCID 178459124HCID 178459124, 화합물

생성물 1

HCID 387447Bortezomib

시약·촉매·용매 2

HCID 887Methanol용매HCID 8900Heptane용매

실험 절차

1N HCl (37.1 mL) was added dropwise into a mixture of pinacol N-(pyrazine-2-yl-carbonyl)-L-phenylalanine-L-leucine boronate ([8]; 5.77 g, 12.4 mmol as a 22.0 (R,S)-[8])/(S,S)-[8] diastereomeric mixture) and 2-methylpropaneboronic acid (1.89 g, 18.5 mmol) in MeOH (57.7 mL) and n-heptane (57.7 mL). The reaction mixture was stirred at room temperature overnight. The water layer was separated and washed twice with n-heptane (30 mL each). The water layer was concentrated at 35° C. and DCM (30 mL) was added into the residue. 2 N NaOH (36.9 mL) was added dropwise into the reaction mixture. The water layer was separated and washed twice with DCM (30 mL each). After dilution with DCM (30 mL) 1N HCl was added dropwise until the pH of the aqueous phase was about 6. The water layer was extracted twice with DCM (30 mL each). The DCM portions were collected together and concentrated at 35° C. Ethyl acetate (46 mL) was added into the residue and concentrated. Ethyl acetate (16 mL) was added into the residue and concentrated until approximately 10% of the original volume remained. n-Heptane (46 mL) was added and the resulting solid was then filtered, washed with n-heptane (20 mL) and dried under vacuum at 35° C. The crude bortezomib was obtained as yellow solid (3.7 g, 9.63 mmol).

후처리

  1. customThe water layer was separated
  2. washwashed twice with n-heptane (30 mL each)
  3. concentrationThe water layer was concentrated at 35° C.
  4. additionDCM (30 mL) was added into the residue
  5. addition2 N NaOH (36.9 mL) was added dropwise into the reaction mixture
  6. customThe water layer was separated
  7. washwashed twice with DCM (30 mL each)
  8. additionAfter dilution with DCM (30 mL) 1N HCl was added dropwise until the pH of the aqueous phase
  9. extractionThe water layer was extracted twice with DCM (30 mL each)
  10. customThe DCM portions were collected together
  11. concentrationconcentrated at 35° C
  12. additionEthyl acetate (46 mL) was added into the residue
  13. concentrationconcentrated
  14. additionEthyl acetate (16 mL) was added into the residue
  15. concentrationconcentrated until approximately 10% of the original volume
  16. additionn-Heptane (46 mL) was added
  17. filtrationthe resulting solid was then filtered
  18. washwashed with n-heptane (20 mL)
  19. customdried under vacuum at 35° C

출처 및 근거

ORD 기록
ord-76240c17e48b46d39de8e2014cee9865
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497374B2

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