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

HRID 2207096Notes

Reaction equation

HRID 2207096 reaction equation
[OH-].[Na+].C([O:6][CH2:7][CH2:8][C@@H:9]([NH:13][C:14]1[C:19]([CH2:20][C:21]2[CH:39]=[CH:38][C:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][C@H:30]3[C:34]([O:36]C)=[O:35])=[CH:23][C:22]=2[O:40][CH3:41])=[C:18]([CH3:42])[N:17]=[C:16]([NH2:43])[N:15]=1)[CH2:10][CH2:11][CH3:12])(=O)C>CO>[NH2:43][C:16]1[N:15]=[C:14]([NH:13][C@@H:9]([CH2:10][CH2:11][CH3:12])[CH2:8][CH2:7][OH:6])[C:19]([CH2:20][C:21]2[CH:39]=[CH:38][C:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][C@H:30]3[C:34]([OH:36])=[O:35])=[CH:23][C:22]=2[O:40][CH3:41])=[C:18]([CH3:42])[N:17]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 117992586(S)-methyl 1-(3-(4-((4-((S)-1-acetoxyhexan-3-ylamino)-2-amino-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylate

Product 1

HCID 89907922(S)-1-(3-(4-((2-amino-4-((S)-1-hydroxyhexan-3-ylamino)-6-methylpyrimidin-5-yl)methyl)-3-methoxyphenoxy)propyl)pyrrolidine-2-carboxylic acidYield 88.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1M-sodium hydroxide (2 mL) was added to a solution of the product (60 mg) from step (vi) in methanol (2 mL) and the mixture was stirred at RT for 9 h. The reaction mixture was concentrated, diluted with water and washed with chloroform. The aqueous layer was neutralized with 2M-hydrogen chloride and extracted with chloroform/EtOH (3/1). The combined organic layer was dried and concentrated. The residue was diluted with chloroform, filtered, concentrated under reduced pressure to afford the sub-title compound (48 mg) as a white solid; 1H NMR (CDCl3); 6.79 (1H, d), 6.48 (1H, d), 6.38 (1H, dd), 6.17 (1H, br s), 5.24 (1H, br s), 4.20-3.97 (3H, m), 3.85 (3H, s), 3.70-3.58 (1H, m), 3.55 (2H, s), 3.48-3.34 (2H, m), 3.32-3.15 (2H, m), 3.05-2.80 (1H, m), 2.75-2.55 (1H, m), 2.35 (3H, s), 2.30-2.07 (4H, m), 2.05-1.85 (2H, m), 1.85-1.70 (1H, m), 1.48-1.34 (1H, m), 1.33-0.98 (4H, m), 0.77 (3H, t); LC-MS: m/z 516.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water
  3. washwashed with chloroform
  4. extractionextracted with chloroform/EtOH (3/1)
  5. customThe combined organic layer was dried
  6. concentrationconcentrated
  7. additionThe residue was diluted with chloroform
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-612841367de0471b9b08db55e6d9bb9a
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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