Dichloromethane → HCID 86730378, compound

HRID 705066Notes

Reaction equation

HRID 705066 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.Br.Br[CH2:11][C:12]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)=O.ClCCl.C(N(CC)CC)C.[OH-].[Na+]>Cl[Ti](Cl)(Cl)Cl.C(Cl)(Cl)Cl>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[N:3]([CH:11]=[C:12]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[N:1]=2)[CH:4]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27377012-Amino-5-fluoropyridineHCID 27762343-(2-Bromoacetyl)pyridine hydrobromide

Product 1

HCID 86730378HCID 86730378, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

2-Amino-5-fluoropyridine (0.048 g, 0.427 mmol), 3-bromoacetylpyridine hydrobromide (0.10 g, 0.356 mmol) and chloroform (3.56 mL) were added to a microwave vial. To the resulting solution were added a solution of TiCl4 in dichloromethane (1.0 M, 0.267 mL, 0.267 mmol) and triethylamine (0.030 mL, 0.214 mmol). The reaction was then heated in a microwave at 110° C. for 30 minutes. The resulting mixture was poured into aqueous sodium hydroxide solution (1.0 N) and extracted with ethyl acetate. The organic extracts were combined, dried over MgSO4, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (50% to 100% ethyl acetate in hexanes) provided the title compound: LCMS m/z 214.09 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.13 (d, J=1.7 Hz, 1H), 8.59-8.58 (m, 1H), 8.29-8.28 (m, 1H), 8.10 (t, J=2.9, 2.9 Hz, 1H), 7.95 (s, 1H), 7.63 (dd, J=9.9, 5.1 Hz, 1H), 7.40 (dd, J=7.9, 5.0 Hz, 1H), 7.18-7.14 (m, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography on silica gel (50% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1d133c7a04b14616b54f32a420fbc601
Source dataset
uspto-grants-2015_11
Patent number
US09173873B2

Reaction notes

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