Hydrochloric Acid → HCID 60197936, compound

HRID 1525842Notes

Reaction equation

HRID 1525842 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[C:26]([C:28]1[CH:29]=[C:30]([O:34][C:35]2[CH:40]=[C:39]([CH3:41])[N:38]=[C:37]([C:42](OC)=[O:43])[CH:36]=2)[CH:31]=[N:32][CH:33]=1)#[N:27].Cl>C1COCC1.CCOC(C)=O>[C:26]([C:28]1[CH:29]=[C:30]([O:34][C:35]2[CH:40]=[C:39]([CH3:41])[N:38]=[C:37]([C:42]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=3)=[O:43])[CH:36]=2)[CH:31]=[N:32][CH:33]=1)#[N:27]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 27377012-Amino-5-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 68295389HCID 68295389, compound

Product 1

HCID 60197936HCID 60197936, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-Amino-5-fluoropyridine (34.3 mg, 0.306 mmol, 1.10 eq) was dissolved in THF (0.7 mL) in a flame-dried round bottom flask. A 0.5 M solution of potassium bis(trimethylsilyl)amide in toluene (0.613 mL, 0.306 mmol, 1.10 eq) was added dropwise and the reaction was stirred for 5 minutes. Methyl 4-(5-cyanopyridin-3-yloxy)-6-methylpicolinate (75 mg, 0.28 mmol, 1.0 eq) was added as a solution in THF (0.7 mL) and the reaction was stirred for 30 minutes. The reaction was diluted with EtOAc, neutralized with 1N HCl, and washed with water. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 45 mg (46%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ 10.48 (s, 1H), 8.99 (s, 1H), 8.87 (d, J=2.4 Hz, 1H), 8.41-8.39 (m, 2H), 8.27 (dd, J=9.1, 4.1 Hz, 1H), 7.86 (td, J=8.7, 2.8 Hz, 1H), 7.56 (d, J=1.7 Hz, 1H), 7.28 (d, J=1.7 Hz, 1H), 2.58 (s, 3H); [M+1]+: 350.2.

Workup

  1. stirringthe reaction was stirred for 30 minutes
  2. washwashed with water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-79e9b3fa37ee435496c3cd4c82c4a7fb
Source dataset
uspto-grants-2015_07
Patent number
US09085562B2

Reaction notes

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