Pyridine → N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-(chloromethyl)-1,3-thiazole-4-carboxamide

HRID 1695741Notes

Reaction equation

HRID 1695741 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:17])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.N1C=CC=CC=1.[Cl:24][CH2:25][C:26]1[S:27][CH:28]=[C:29]([C:31](Cl)=[O:32])[N:30]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([NH:17][C:31]([C:29]2[N:30]=[C:26]([CH2:25][Cl:24])[S:27][CH:28]=2)=[O:32])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2

Participants

6

Reactant 4

HCID 1049PyridineHCID 516892Sodium BicarbonateHCID 582557836-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amineHCID 597024562-(Chloromethyl)-1,3-thiazole-4-carbonyl chloride

Product 1

HCID 58255786N-[6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-(chloromethyl)-1,3-thiazole-4-carboxamideYield 67.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (1.47 g) in DCM (20 ml) was added pyridine (1 ml). The reaction mixture was stirred for 5 minutes at room temperature before 2-(chloromethyl)-1,3-thiazole-4-carbonyl chloride (1.21 g) in DCM (20 ml) was added dropwise over 10 minutes. The reaction mixture was stirred at room temperature for 18 hours. Saturated sodium bicarbonate solution (40 ml) was added and the reaction was stirred vigorously before the organic layer was separated using a hydrophobic frit. The aqueous layer was extracted with further DCM and the combined organic layers were evaporated to dryness. The residual solid was dried on a high vacuum line before triturating with cyclohexane to give the title compound (1.52 g).

Workup

  1. additionwas added dropwise over 10 minutes
  2. stirringthe reaction was stirred vigorously before the organic layer
  3. customwas separated
  4. extractionThe aqueous layer was extracted with further DCM
  5. customthe combined organic layers were evaporated to dryness
  6. customThe residual solid was dried on a high vacuum line
  7. custombefore triturating with cyclohexane

Sources & evidence

ORD record
ord-da4ba152ae204accaca5ff5c985e463e
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

Loading…