Pyridine → HCID 178418902, compound

HRID 710111Notes

Reaction equation

HRID 710111 reaction equation
[OH:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.N1C=CC=CC=1.[F:16][C:17]([F:28])([F:27])[C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1>C(Cl)Cl.O>[Br:9][C:5]1[CH:6]=[C:7]([NH:8][C:22](=[O:23])[C:21]2[CH:25]=[CH:26][C:18]([C:17]([F:16])([F:27])[F:28])=[CH:19][CH:20]=2)[C:2]([OH:1])=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 178418959HCID 178418959, compound

Product 1

HCID 178418902HCID 178418902, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4-(Trifluoromethyl)benzoic acid (2.45 g, 12.9 mmol) dissolved in DCM (30 ml), cooled to 0° C. and added oxalyl chloride (3.4 ml, 38.6 mmol). Catalytic amount of DMF was added to this mixture and stirred at rt for 30 mins. After 30 mins, DCM removed on rotavapour and co-distilled the residue two times with DCM to obtain 4-(trifluoromethyl)benzoyl chloride quantitatively. 2-Hydroxy-3-amino-5-bromopyridine (2.4 g, 11.1 mmol) dissolved in DCM (15 ml) and added Pyridine (1.74 g, 22 mmol) under nitrogen atmosphere. This mixture stirred at rt for 30 mins and added 4-(trifluoromethyl)benzoyl chloride (2.4 g, 13.3 mmol). After continuing stirring at rt for 30 mins, reaction mass diluted with water and extracted with DCM. DCM removed on rotavapour to obtain the crude. Crude was purified on column using 60-120 mesh silica gel and a gradient mixture of MeOH and DCM (2:98) as eluent to afford the titled compound (2.1 g) as a brown solid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 12.43 (bs, 1H), 9.58 (s, 1H), 8.37 (d, J 2.6, 1H), 8.09 (d, J 8.2, 2H), 7.91 (d, J 8.2, 2H), 7.48 (d, J 2.6, 1H).

Workup

  1. stirringAfter continuing stirring at rt for 30 mins
  2. customreaction mass
  3. extractionextracted with DCM
  4. customDCM removed on rotavapour
  5. customto obtain the crude
  6. customCrude was purified on column
  7. additiona gradient mixture of MeOH and DCM (2:98) as eluent

Sources & evidence

ORD record
ord-fd92713ace0142e488cdac67c4a8acc1
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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