Tetraethylammonium fluoride dihydrate → HCID 118036955, compound

HRID 1777972Notes

Reaction equation

HRID 1777972 reaction equation
[C:1]([C:3]1[C:4]([NH:44][CH2:45][CH2:46][O:47][CH3:48])=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[N:20]=[C:19]([CH:22]([O:25][CH3:26])[O:23][CH3:24])[C:18]([CH2:27][N:28]4[CH2:33][CH2:32][N:31](C(OCC[Si](C)(C)C)=O)[CH2:30][C:29]4=[O:43])=[CH:17][C:16]=3[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2].O.O.[F-].C([N+](CC)(CC)CC)C>C(C#N)(C)=O>[C:1]([C:3]1[C:4]([NH:44][CH2:45][CH2:46][O:47][CH3:48])=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([CH2:27][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][C:29]4=[O:43])=[C:19]([CH:22]([O:25][CH3:26])[O:23][CH3:24])[N:20]=3)[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 2776564Tetraethylammonium fluoride dihydrateHCID 131734789HCID 131734789, compound2×

Product 1

HCID 118036955HCID 118036955, compound

Reagents, catalysts & solvents 1

HCID 694302-OxopropiononitrileSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(trimethylsilyl)ethyl 4-((8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-3-oxopiperazine-1-carboxylate (intermediate 122, 4.20 g, 5.29 mmol) and tetraethylammonium fluoride dihydrate (2.53 g, 13.22 mmol) in AcCN (50 ml) was heated for 30 minutes at 70° C. The reaction mixture was partitioned between saturated aqueous NaHCO3 solution and DCM, the DCM phase washed with brine, dried over MgSO4 and evaporated. The residue was applied to a RediSep® silica column and purified by normal phase chromatography, eluting with EtOAc then a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a yellow-white solid. (UPLC-MS 7) tR 0.68; ESI-MS 539.5 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 solution and DCM
  2. washthe DCM phase washed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. custompurified by normal phase chromatography
  6. washeluting with EtOAc
  7. additionProduct containing fractions
  8. customevaporated

Sources & evidence

ORD record
ord-63b643ad79e148949c4b601bbe45b2b2
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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