Trifluoroacetic acid → (R)-1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylic acid

HRID 2207089노트

반응식

HRID 2207089 반응식
FC(F)(F)C(O)=O.[NH2:8][C:9]1[N:14]=[C:13]([NH:15][C@@H:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][OH:19])[C:12]([CH2:23][C:24]2[CH:45]=[CH:44][C:27]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][CH2:34][C@@H:33]3[C:37]([O:39]C(C)(C)C)=[O:38])=[CH:26][C:25]=2[O:46][CH3:47])=[C:11]([CH3:48])[N:10]=1>>[NH2:8][C:9]1[N:14]=[C:13]([NH:15][C@@H:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][OH:19])[C:12]([CH2:23][C:24]2[CH:45]=[CH:44][C:27]([O:28][CH2:29][CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][CH2:34][C@@H:33]3[C:37]([OH:39])=[O:38])=[CH:26][C:25]=2[O:46][CH3:47])=[C:11]([CH3:48])[N:10]=1

참가 물질

3

반응물 2

HCID 6422Trifluoroacetic acidHCID 117992620(R)-tert-butyl 1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methyl pyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

생성물 1

HCID 72549037(R)-1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylic acid수율 98.8%

실험 절차

Trifluoroacetic acid (6 mL) was added to the product from step (x) (505 mg) and the mixture was stirred at RT for 14 h. After the reaction mixture was concentrated, 1M-sodium hydroxide (20 mL) and methanol (10 mL) was added to the residue and the mixture was stirred in methanol for 30 mins. The reaction mixture was concentrated, diluted with water and washed with chloroform. The aqueous layer was neutralized with 6M-hydrogen chloride and sat. sodium hydrogen dicarbonate and extracted with chloroform/EtOH (3/1). The combined organic layer was dried and concentrated. The residue was diluted with chloroform, filtered, concentrated and diluted with chloroform/EtOAc. The precipitate was collected by filtration, washed with EtOAc and dried to give 450 mg of the sub-title compound as a white solid; 1H NMR (CDCl3); 6.78 (1H, d), 6.48 (1H, d), 6.38 (1H, dd), 5.35-5.20 (1H, m), 4.20-3.97 (3H, m), 3.86 (3H, s), 3.55 (2H, s), 3.63-3.47 (1H, m), 3.40-3.09 (4H, m), 2.91-2.75 (1H, m), 2.60-2.45 (1H, m), 2.35 (3H, s), 2.30-2.02 (4H, m), 2.02-1.70 (3H, m), 1.50-1.33 (1H, m), 1.33-0.95 (5H, m), 0.77 (3H, t); LC-MS: m/z 516.

후처리

  1. concentrationAfter the reaction mixture was concentrated
  2. addition1M-sodium hydroxide (20 mL) and methanol (10 mL) was added to the residue
  3. stirringthe mixture was stirred in methanol for 30 mins
  4. concentrationThe reaction mixture was concentrated
  5. additiondiluted with water
  6. washwashed with chloroform
  7. extractionextracted with chloroform/EtOH (3/1)
  8. customThe combined organic layer was dried
  9. concentrationconcentrated
  10. additionThe residue was diluted with chloroform
  11. filtrationfiltered
  12. concentrationconcentrated
  13. additiondiluted with chloroform/EtOAc
  14. filtrationThe precipitate was collected by filtration
  15. washwashed with EtOAc
  16. customdried

출처 및 근거

ORD 기록
ord-e9fc0898e23443df9127eadeb46a600c
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09376398B2

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