L-Tyrosine → (S)-2-Amino-3-(3-((2-aminothiazol-5-yl)methyl)-4-hydroxyphenyl)propanoic acid

HRID 1755454노트

반응식

HRID 1755454 반응식
[NH2:1][C:2]1[S:3][C:4]([CH2:7]O)=[CH:5][N:6]=1.[NH2:9][C@H:10]([C:19]([OH:21])=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.FC(F)(F)S(O)(=O)=O>[N+](C)([O-])=O>[NH2:9][C@@H:10]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([OH:18])=[C:16]([CH2:7][C:4]2[S:3][C:2]([NH2:1])=[N:6][CH:5]=2)[CH:17]=1)[C:19]([OH:21])=[O:20]

참가 물질

5

반응물 3

HCID 6057L-TyrosineHCID 62406Trifluoromethanesulfonic acidHCID 11217273(2-Aminothiazol-5-yl)methanol

생성물 1

HCID 86700104(S)-2-Amino-3-(3-((2-aminothiazol-5-yl)methyl)-4-hydroxyphenyl)propanoic acid수율 61.7%

시약·촉매·용매 1

HCID 6375Nitromethane용매

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온도
80 °C

실험 절차

To a suspension of (2-aminothiazol-5-yl)methanol (35 mg, 0.269 mmol) and L-Tyrosine (199.6 mg, 1.102 mmol) in nitromethane (3.00 mL) is added trifluoromethanesulfonic acid (170 μL, 1.914 mmol). The resulting solution is sonicated for 15 sec, then heated at 80° C. for 18 h. The reaction is evaporated to dryness and the residue is purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 0% Solvent B to 60% Solvent B over 12 min, ret. T=5.14 min. The product fractions are poured thru a washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge and washed with additional MeOH (50 mL). Elution with Aldrich 2.0M NH3/MeOH (20 mL) followed by evaporation gives 48.7 mg (55.6%) of the title compound as a light tan solid. LC/MS (Condition A): ret. T=0.63 min, (M+H)+ 294.05. Analytical HPLC: (Condition C): >95%, ret. T=3.26 min, (Condition D): >90%, ret. T=3.00 min. 1H NMR (500 MHz, DMSO-d6+D2O) δ ppm 6.86-7.04 (2 H, m), 6.67-6.76 (1 H, m), 6.58-6.67 (1 H, m), 3.74 (2 H, br. s.), 3.33 (1 H, br. s.), 3.02 (1 H, d, f=10.07 Hz), 2.68 (1 H, br. s.).

후처리

  1. customThe resulting solution is sonicated for 15 sec
  2. customThe reaction is evaporated to dryness
  3. customthe residue is purified by preparative HPLC (Condition A)
  4. customover 12 min
  5. customT=5.14 min
  6. additionThe product fractions are poured thru
  7. extractiona washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge
  8. washwashed with additional MeOH (50 mL)
  9. washElution with Aldrich 2.0M NH3/MeOH (20 mL)
  10. customfollowed by evaporation

출처 및 근거

ORD 기록
ord-f925647a03484bdaa4bd6d74ff781485
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169295B2

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