Sodium hydride → 4-[(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholine

HRID 1710790Notes

Reaction equation

HRID 1710790 reaction equation
[H-].[Na+].[CH3:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][CH2:10][CH2:11][OH:12].Cl[C:14]1[N:19]=[CH:18][C:17]([C:20]2[S:21][C:22]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[C:23]([CH3:25])[N:24]=2)=[CH:16][CH:15]=1>CN(C)C=O>[CH3:25][C:23]1[N:24]=[C:20]([C:17]2[CH:18]=[N:19][C:14]([O:12][CH2:11][CH2:10][CH2:9][N:5]3[CH2:6][CH2:7][CH2:8][CH:4]3[CH3:3])=[CH:15][CH:16]=2)[S:21][C:22]=1[C:26]([N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)=[O:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 224016093-(2-Methylpyrrolidin-1-yl)propan-1-olHCID 594574974-{[2-(6-Chloropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]carbonyl}morpholine

Product 1

HCID 594575194-[(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholineYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride 60% in oil (0.11 g, 2.2 eq, 2.82 mmol) is added to a mixture of 3-(2-methyl-1-pyrrolidinyl)-1-propanol (0.31 g, 2.2 eq, 2.18 mmol) in dimethylformamide (15 ml) cooled to 0° C. The mixture is stirred at 22° C. for 20 min, and cooled again to 0° C. 4-{[2-(6-chloropyridin-3-yl)-4-methyl-1,3-thiazol-5-yl]carbonyl}morpholine i99 (0.415 g, 1 eq, 1.28 mmol) is then added to the solution and the mixture is stirred 48 h at room temperature. The solvent is evaporated, and the residue is taken up in ethyl acetate and washed two times with an aqueous solution of sodium hydrogenocarbonate. The organic layer is dried over magnesium sulfate, filtered and concentrated under vacuum. Purification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 97/2.7/0.3) affords 0.047 g of 4-[(4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-1,3-thiazol-5-yl)carbonyl]morpholine 147.

Workup

  1. temperaturecooled again to 0° C
  2. stirringthe mixture is stirred 48 h at room temperature
  3. customThe solvent is evaporated
  4. washwashed two times with an aqueous solution of sodium hydrogenocarbonate
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 97/2.7/0.3)

Sources & evidence

ORD record
ord-6c0f031bc20f421bbbcb20c5823d8696
Source dataset
uspto-grants-2010_09
Patent number
US07790720B2

Reaction notes

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