Diisopropylethylamine → Ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(4-(2-(methylamino)-2-oxoethyl)thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

HRID 524649Notes

Reaction equation

HRID 524649 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH3:20])[NH:12][C:11]([C:21]2[S:22][CH:23]=[C:24]([CH2:26][C:27]([OH:29])=O)[N:25]=2)=[N:10]1.C[CH2:31][N:32]=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.CN>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH3:20])[NH:12][C:11]([C:21]2[S:22][CH:23]=[C:24]([CH2:26][C:27]([NH:32][CH3:31])=[O:29])[N:25]=2)=[N:10]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 1181076312-(2-(4-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-6-methyl-1,4-dihydropyrimidin-2-yl)thiazol-4-yl)acetic acid

Product 1

HCID 118107527Ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-(4-(2-(methylamino)-2-oxoethyl)thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylateYield 39.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of 2-(2-(4-(2-bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-6-methyl-1,4-dihydropyrimidin-2-yl)thiazol-4-yl)acetic acid (3 g, 6.2 mmol), EDC.HCl (1.55 g, 8.06 mmol), HOAt (0.84 g, 6.2 mmol) and DIPEA (1.6 g, 12.4 mmol) in DMF (60 mL) was cooled to 10° C. and then stirred at −10° C. for 30 minutes. Then methanamine hydrochloride (0.63 g, 9.3 mmol) was added and the mixture was stirred for another 1 hour. The mixture was warmed to 50° C. and stirred for 4 hours. The reaction solution was diluted with EtOAc (150 mL), and washed with brine (100 mL×6). The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=3/1) to give the title compound as a yellow solid (1.2 g, 39%). The compound was characterized by the following spectroscopic data:

Workup

  1. stirringthe mixture was stirred for another 1 hour
  2. temperatureThe mixture was warmed to 50° C.
  3. stirringstirred for 4 hours
  4. washwashed with brine (100 mL×6)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=3/1)

Sources & evidence

ORD record
ord-27f68f28f390493cad5d572cec529e2b
Source dataset
uspto-grants-2016_05
Patent number
US09340538B2

Reaction notes

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