Morpholine → 2-[(4-{2-[(5-Ethylpyrimidin-2-yl)(4-morpholin-4-ylbenzyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

HRID 914497Notes

Reaction equation

HRID 914497 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[C:28]([O:32][C:33](=[O:62])[C:34]([S:37][C:38]1[S:39][CH:40]=[C:41]([CH2:43][CH2:44][N:45]([CH2:54][C:55]2[CH:60]=[CH:59][C:58](Br)=[CH:57][CH:56]=2)[C:46]2[N:51]=[CH:50][C:49]([CH2:52][CH3:53])=[CH:48][N:47]=2)[N:42]=1)([CH3:36])[CH3:35])([CH3:31])([CH3:30])[CH3:29].[NH:63]1[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:28]([O:32][C:33](=[O:62])[C:34]([S:37][C:38]1[S:39][CH:40]=[C:41]([CH2:43][CH2:44][N:45]([C:46]2[N:51]=[CH:50][C:49]([CH2:52][CH3:53])=[CH:48][N:47]=2)[CH2:54][C:55]2[CH:60]=[CH:59][C:58]([N:63]3[CH2:68][CH2:67][O:66][CH2:65][CH2:64]3)=[CH:57][CH:56]=2)[N:42]=1)([CH3:36])[CH3:35])([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 597592542-[(4-{2-[(4-Bromobenzyl)(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597589862-[(4-{2-[(5-Ethylpyrimidin-2-yl)(4-morpholin-4-ylbenzyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl esterYield 49.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

tris(Dibenzylideneacetone)dipalladium (32 mg), 2-(di-tert-butylphosphino)biphenyl (21 mg) and sodium tert-butoxide (73 mg) were added to a 20 mL screw cap test tube substituted with nitrogen, and a solution of 2-[(4-{2-[(4-bromobenzyl)(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (400 mg) synthesized in Example 402-1 and morpholine (91 mg) in toluene (1.4 mL) was added thereto. The test tube was capped, and stirred at 110° C. for 8 hr. After cooling to room temperature, the solution was directly purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=3:1 to 2:1) to give the title compound (200 mg) as a colorless oil.

Workup

  1. customcap test tube
  2. customThe test tube was capped
  3. temperatureAfter cooling to room temperature
  4. customthe solution was directly purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=3:1 to 2:1)

Sources & evidence

ORD record
ord-4ad6bc93c9c34e318f2f4c7cd84f8df6
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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