Sodium hydride → (4-ethyl-1,3-thiazol-2(3H)-ylidene)(2-{[4-(morpholin-4-ylmethyl)benzyl]oxy}pyrimidin-4-yl)acetonitrile

HRID 2375321Notes

Reaction equation

HRID 2375321 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]1[CH:17]=[CH:16][C:8]([CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:7][CH:6]=1.Cl[C:19]1[N:24]=[C:23]([C:25](=[C:28]2[NH:32][C:31]([CH2:33][CH3:34])=[CH:30][S:29]2)[C:26]#[N:27])[CH:22]=[CH:21][N:20]=1>C(#N)C>[CH2:33]([C:31]1[NH:32][C:28](=[C:25]([C:23]2[CH:22]=[CH:21][N:20]=[C:19]([O:3][CH2:4][C:5]3[CH:6]=[CH:7][C:8]([CH2:9][N:10]4[CH2:15][CH2:14][O:13][CH2:12][CH2:11]4)=[CH:16][CH:17]=3)[N:24]=2)[C:26]#[N:27])[S:29][CH:30]=1)[CH3:34]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2795499[4-(Morpholinomethyl)phenyl]methanolHCID 72996219HCID 72996219, compound

Product 1

HCID 69310028(4-ethyl-1,3-thiazol-2(3H)-ylidene)(2-{[4-(morpholin-4-ylmethyl)benzyl]oxy}pyrimidin-4-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

To a suspension of NaH (99 mg, 2.27 mmol) in ACN (4 mL) was added a solution of N-(4-hydroxymethylbenzyl)morpholine 313 mg, 1.51 mmol) in ACN (4 mL). The mixture was stirred 1 h at rt. Then (2-chloropyrimidin-4-yl)(4-ethyl-1,3-thiazol-2(3H)-ylidene)acetonitrile (200 mg, 0.76 mmol) was added portion wise. The resulting mixture was heated up at 80° C. for 5 h. After cooling down to rt the ACN was evaporated. EtOAc (5 mL) was added to the residue. After one night at 4° C., the yellow solid was filtered off affording the title compound as a free base (HPLC (max plot) 73.9%). The solid was taken up in DCM and excess TFA then ether were added. The precipitate formed was filtered off, washed with ether (3×) then dried under reduced pressure at 40° C. overnight, affording 409 mg of the title compound as a diTFA salt (Yellow powder, Y=81.1%)

Workup

  1. temperatureThe resulting mixture was heated up at 80° C. for 5 h
  2. customwas evaporated
  3. additionEtOAc (5 mL) was added to the residue
  4. waitAfter one night at 4° C.
  5. filtrationthe yellow solid was filtered off

Sources & evidence

ORD record
ord-e4a3774928c8410b90204e1a22f2b4c3
Source dataset
uspto-grants-2008_12
Patent number
US07465736B2

Reaction notes

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