Tetrabutylammonium Fluoride → (S)-3-(2-amino-5-(4-(3-hydroxypropoxy)-2-methoxybenzyl)-6-m ethylpyrimidin-4-yl-amino)hexyl acetate

HRID 2207093Notes

Reaction equation

HRID 2207093 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([O:22][CH2:23][CH2:24][C@@H:25]([NH:29][C:30]1[C:35]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46][O:47][Si](C(C)(C)C)(C)C)=[CH:39][C:38]=2[O:55][CH3:56])=[C:34]([CH3:57])[N:33]=[C:32]([NH2:58])[N:31]=1)[CH2:26][CH2:27][CH3:28])(=[O:21])[CH3:20]>C1COCC1.O.C(=O)([O-])O.[Na+]>[C:19]([O:22][CH2:23][CH2:24][C@@H:25]([NH:29][C:30]1[C:35]([CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH2:46][OH:47])=[CH:39][C:38]=2[O:55][CH3:56])=[C:34]([CH3:57])[N:33]=[C:32]([NH2:58])[N:31]=1)[CH2:26][CH2:27][CH3:28])(=[O:21])[CH3:20]

Participants

6

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89907092(S)-3-(2-amino-5-(4-(3-(tert-butyldimethylsilyloxy)propoxy)-2-methoxybenzyl)-6-methylpyrimidin-4-ylamino)hexyl acetate

Product 1

HCID 89907823(S)-3-(2-amino-5-(4-(3-hydroxypropoxy)-2-methoxybenzyl)-6-m ethylpyrimidin-4-yl-amino)hexyl acetate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Tetra-n-butylammonium fluoride (561 mg) was added to the mixture of the product from step (iii) in THF (14 mL). After the mixture was stirred at RT for 1.5 h, the reaction mixture was diluted with water and sat. sodium hydrogen carbonate and extracted with EtOAc. The combined organic layer was washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash column chromatography on amino silica gel to afford the sub-title compound (660 mg) as a colourless oil; 1H NMR (CDCl3); 6.82 (1H, d), 6.45 (1H, d), 6.39 (1H, dd), 4.71 (2H, br s), 4.23-4.13 (1H, m), 4.07 (2H, t), 3.85 (3H, s), 3.85-3.74 (4H, m), 3.58 (2H, s), 2.33 (3H, s), 2.15 (1H, br s), 2.04-1.97 (2H, m), 1.97 (3H, s), 1.88-1.75 (1H, m), 1.60-1.47 (1H, m), 1.45-1.32 (1H, m), 1.31-1.19 (1H, m), 1.17-1.03 (2H, m), 0.79 (3H, t); LC-MS: m/z 461.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on amino silica gel

Sources & evidence

ORD record
ord-cc80becad6b546fd88c335ed98991a1b
Source dataset
uspto-grants-2016_06
Patent number
US09376398B2

Reaction notes

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