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 2207089ノート

反応式

HRID 2207089 の反応式
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

参加物

3

反応物 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

生成物 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 acid収率 98.8%

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e9fc0898e23443df9127eadeb46a600c
出典データセット
uspto-grants-2016_06
特許番号
US09376398B2

反応ノート

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