2-Bromoethanol → 2-{4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1H-pyrazol-1-yl}ethanol

HRID 1040150Notes

Reaction equation

HRID 1040150 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:5]=[C:6]([C:8]2[S:12][C:11]([C:13]3[CH:14]=[N:15][NH:16][CH:17]=3)=[N:10][CH:9]=2)[CH:7]=1.[H-].[Na+].Br[CH2:32][CH2:33][OH:34]>CN(C=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][C:11]([C:13]3[CH:17]=[N:16][N:15]([CH2:32][CH2:33][OH:34])[CH:14]=3)=[N:10][CH:9]=2)[CH:5]=[C:4]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:22]=[CH:21][N:20]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 108982-BromoethanolHCID 24758Sodium hydrideHCID 58456134N-{3-methyl-5-[2-(1H-pyrazol-4-yl)-1,3-thiazol-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 584563002-{4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1H-pyrazol-1-yl}ethanolYield 6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a sealed tube was added N-{3-methyl-5-[2-(1H-pyrazol-4-yl)-1,3-thiazol-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine (38.0 mg, 0.095 mmol), DMF (950 μL, 0.1 M) and NaH (15.0 mg, 0.380 mmol, 60% wt). The reaction was allowed to age for 20 minutes. Next was added 2-bromo ethanol (11.8 mg, 0.095 mmol) and the reaction was allowed to stir at rt for 4 hours. The completed reaction was quenched with H2O (100 μL) and was concentrated in vacuo. Purification by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier) to afford the title product (2.8 mg, 0.0057 mmol, 6.0%). MS ESI: [M+H]+ m/z 447.1. 1H NMR (600 MHz, DMSO) δ 10.24 (s, 1H), 8.82 (d, J=4.9, 1H), 8.28 (s, 1H), 8.01 (s, 1H), 7.97 (s, 1H), 7.91 (s, 1H), 7.44 (s, 1H), 7.26 (d, J=4.9, 1H), 7.16 (s, 1H), 4.18 (t, J=5.5, 2H), 3.74 (s, 2H), 2.30 (s, 3H). rhSTK activity=+++

Workup

  1. customThe completed reaction
  2. customwas quenched with H2O (100 μL)
  3. concentrationwas concentrated in vacuo
  4. customPurification by reverse phase preparative HPLC (0:100 to 95:5 acetonitrile:water: 0.1% v/v formic acid modifier)

Sources & evidence

ORD record
ord-db4332a5acbd4fca871282ee1d9798d3
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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