Diisopropylethylamine → N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

HRID 244635

Reaction equation

HRID 244635 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([OH:9])=O)[N:6]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Br:43][C:44]1[CH:45]=[C:46]([NH2:53])[C:47]2[CH:48]=[N:49][NH:50][C:51]=2[CH:52]=1>CN(C=O)C>[Br:43][C:44]1[CH:52]=[C:51]2[C:47]([CH:48]=[N:49][NH:50]2)=[C:46]([NH:53][C:7]([C:5]2[N:6]=[C:2]([CH3:1])[S:3][CH:4]=2)=[O:9])[CH:45]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2847282-Methyl-1,3-thiazole-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 247280636-Bromo-1H-indazol-4-amine

Product 1

HCID 58255750N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamideYield 18.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

2-Methyl-1,3-thiazole-4-carboxylic acid (4.59 g) (available from Maybridge), HATU (13.41 g) and DIPEA (16.80 ml) were stirred in DMF (140 ml) for 30 min at 20° C. 6-Bromo-1H-indazol-4-amine (3.4 g) (available from Sinova) was added and the reaction stirred at 20° C. for 2 days. The solvent was reduced to ˜40 ml and the reaction mixture was applied across 5×70 g aminopropyl SPE cartridges and left to stand for 3 h. The cartridges were eluted with DCM:methanol (1:1) and the combined solvent was evaporated in vacuo. The residue was suspended in DCM:methanol, adsorbed onto Florisil® and purified by chromatography on silica gel (100 g cartridge) eluting with 0-15% gradient of methanol (containing 1% triethylamine) in DCM over 60 min to give title compound (1.02 g).

Workup

  1. waitleft
  2. waitto stand for 3 h
  3. washThe cartridges were eluted with DCM:methanol (1:1)
  4. customthe combined solvent was evaporated in vacuo
  5. custompurified by chromatography on silica gel (100 g cartridge)
  6. washeluting with 0-15% gradient of methanol (containing 1% triethylamine) in DCM over 60 min

Sources & evidence

ORD record
ord-a9afde083cea40e7829cf979ee997c21
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Linked notes

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