Hydrochloric Acid → HCID 67236730, compound

HRID 2401500Notes

Reaction equation

HRID 2401500 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[Cl:26][C:27]1[CH:28]=[C:29]([CH:34]=[C:35]([O:37][C:38]2[CH:39]=[N:40][CH:41]=[N:42][CH:43]=2)[CH:36]=1)[C:30](OC)=[O:31].Cl>C1COCC1.CCOC(C)=O>[Cl:26][C:27]1[CH:28]=[C:29]([CH:34]=[C:35]([O:37][C:38]2[CH:43]=[N:42][CH:41]=[N:40][CH:39]=2)[CH:36]=1)[C:30]([NH:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][N:3]=1)=[O:31]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 183278082-Amino-4-fluoropyridineHCID 58318886HCID 58318886, compound

Product 1

HCID 67236730HCID 67236730, compoundYield 38.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-Amino-4-fluoropyridine (254 mg, 2.27 mmol, 2.00 eq) was dissolved in THF (2.5 mL) in a flame-dried round bottom flask. A 0.5 M solution of potassium bis(trimethylsilyl)amide in toluene (4.76 mL, 2.27 mmol, 2.00 eq) was added dropwise and the reaction was stirred for 5 min. Compound 7 (300 mg, 1.13 mmol, 1.00 eq) was added as a solution in THF (2.5 mL) and the reaction was stirred for 30 min. 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 150 mg (38%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 11.12 (s, 1H), 9.07 (s, 1H), 8.75 (s, 2H), 8.39 (d, J=3.0 Hz, 1H), 8.16 (dd, J=5.0, 4.2 Hz, 1H), 7.88 (t, J=1.6 Hz, 1H), 7.80 (td, J=8.7, 31. Hz, 1H), 7.68 (t, J=2.0 Hz, 1H), 7.58 (t, J=2.1 Hz, 1H); [M+1]+: 345.2

Workup

  1. stirringthe reaction was stirred for 30 min
  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-ae280ab13f214e60b909b1c3cb06e0e2
Source dataset
uspto-grants-2014_08
Patent number
US08796295B2

Reaction notes

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