2,3-Dihydroxybutanedioic Acid → Dobutamine tartrate

HRID 246859

반응식

HRID 246859 반응식
[CH3:1][CH:2]([NH:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([OH:22])=[C:19]([OH:21])[CH:20]=1)[CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([OH:11])=[CH:9][CH:10]=1.OCC(CO)(CO)N.[OH-].[Na+].OS([O-])=O.[Na+].CC(NCCC1C=CC(O)=C(O)C=1)CCC1C=CC(O)=CC=1.Cl.[C:61]([OH:70])(=[O:69])[CH:62]([CH:64]([C:66]([OH:68])=[O:67])[OH:65])[OH:63].C(C(C(C([O-])=O)O)O)([O-])=O>O>[CH3:1][CH:2]([NH:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([OH:22])=[C:19]([OH:21])[CH:20]=1)[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[C@@H:62]([OH:63])([C:61]([OH:70])=[O:69])[C@H:64]([OH:65])[C:66]([OH:68])=[O:67]

참가 물질

9

반응물 7

HCID 8752,3-Dihydroxybutanedioic AcidHCID 6503Tris(hydroxymethyl)aminomethaneHCID 14798Sodium HydroxideHCID 36811Dobutamine3회HCID 65324Dobutamine HydrochlorideHCID 38061142,3-DihydroxybutanedioateHCID 23665763Sodium Bisulfite2회

생성물 1

HCID 208850Dobutamine tartrate

시약·촉매·용매 1

HCID 962Water용매2회

실험 절차

A preferred method of preparing dobutamine free base involves the use of tris(hydroxymethyl)methylamine in place of aqueous sodium hydroxide. A typical preparation using this procedure is carried out as follows: 500 ml of deoxygenated water for injection (WFI) are placed in a 2 1 3-neck round-bottom flask equipped with N2 inlet, dropping funnel, stirring means and a probe leading to a pH meter. A nitrogen sweep is maintained throughout the operation. 50 mg of NaHSO3 are added and the mixture stirred till solution occurs. 80.16 g of dobutamine hydrochloride are added via a y-tube adapter, and any salt remaining in the addition tube is washed in with an additional 500 ml of deoxygenated water (WFI). The resulting slurry is stirred for 15-20 minutes. 250 ml of 1M aqueous tris(hydroxymethyl) methylamine [30.3 g in 250 ml of deoxygenated water (WFI)] are added in dropwise fashion over a 1-2 hr. period at such a rate that the pH of the solution does not rise above pH=8.5. After the addition is completed, the neutralization mixture is chilled to a temperature in the range 0°-10° C. The chilled solution is then vacuum filtered under N2. The filter cake comprising dobutamine free base is washd with 1200 ml of deoxygenated water (WFI) (in three 400 ml portions). Next, a solution is prepared in a 2 1 beaker by dissolving 35.56 g of (+)-tartaric acid and 1.3 g of NaHSO3 in 1 1 of deoxygenated water (WFI). The filter cake is added with stirring to this solution under N2. After the dobutamine free base has all dissolved, the solution is assayed for dobutamine by UV and the volume of solution now containing the (+)-tartrate salt is adjusted by adding deoxygenated water (WFI) such that the final dobutamine concentration is 50 mg./ml. Five milliliter aliquots are then transferred under N2 to a series of vials. The vials under N2 can be sealed as such or lyophilized and then sealed.

후처리

  1. customA typical preparation
  2. customequipped with N2 inlet
  3. temperatureA nitrogen sweep is maintained throughout the operation
  4. stirringthe mixture stirred till solution
  5. washis washed in with an additional 500 ml of deoxygenated water (WFI)
  6. stirringThe resulting slurry is stirred for 15-20 minutes
  7. addition250 ml of 1M aqueous tris(hydroxymethyl) methylamine [30.3 g in 250 ml of deoxygenated water (WFI)] are added in dropwise fashion over a 1-2 hr
  8. additionAfter the addition
  9. temperaturethe neutralization mixture is chilled to a temperature in the range 0°-10° C
  10. filtrationvacuum filtered under N2
  11. customNext, a solution is prepared in a 2 1 beaker
  12. additionThe filter cake is added
  13. stirringwith stirring to this solution under N2
  14. additionby adding
  15. customdeoxygenated water (WFI) such that the final dobutamine concentration is 50 mg
  16. customThe vials under N2 can be sealed as such or lyophilized and
  17. customthen sealed

출처 및 근거

ORD 기록
ord-bd88460ee3c74efcbafa5075673b136d
출처 데이터셋
uspto-grants-1987_11
특허 번호
US04704407

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