Cesium carbonate → 2-(1-((5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1923077Notes

Reaction equation

HRID 1923077 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH2:28]([C:30]1[NH:34][C:33]2[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=2[N:31]=1)[CH3:29].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.CO.S1C=CC=C1C([O-])=O.[Cu+]>[CH2:28]([C:30]1[N:31]([C:2]2[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]4)[S:8][C:6]=3[N:7]=2)[C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1)[CH3:29]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 596055142-(1-((5-Chloro-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 596061422-(1-((5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olYield 36%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture 2-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (100 mg, 0.24 mmol), 2-ethyl-1H-benzoimidazole (42 mg, 0.29 mmol), copper(I) thiophene-2-carboxylate (9 mg, 0.048 mmol) and cesium carbonate (119 mg, 0.36 mmol) in NMP (0.5 mL) was stirred at 110° C. for 18 hours. The reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with MeOH and the desired product was eluted with 2M NH3 in MeOH. The solvents were removed and the residue was subjected to flash chromatography (Si—PCC, 0-20% MeOH in EtOAc) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 332 as a beige solid (45 mg, 36%). LCMS (Method G): RT 7.37 min; [M+H]+ 522. 1H NMR (400 MHz, CHCl3-d): δ 8.03-7.98 (m, 1 H); 7.77-7.73 (m, 1 H); 7.32-7.24 (m, 2 H); 4.41 (m, 4H); 3.90-3.85 (m, 6 H); 3.35 (q, J=7.5 Hz, 2 H); 3.11 (m, 2 H); 2.33-2.12 (m, 2 H); 1.79 (m, 2 H); 1.57 (m, 2 H); 1.44 (t, J=7.5 Hz, 3 H); 1.34 (m, 1 H); 1.22 (s, 6 H)

Workup

  1. washThe cartridge was washed with MeOH
  2. washthe desired product was eluted with 2M NH3 in MeOH
  3. customThe solvents were removed

Sources & evidence

ORD record
ord-4c83eea1b68c4d2f8e56467dfb789b3a
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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