Sodium Carbonate → Ethyl 4-tert-Butyl-2-((2-methyl-3-(4-methyl-6-(4-(morpholine-4-carbonyl)phenyl amino)-5-oxo-4,5-dihydropyrazin-2yl)phenylamino)methyl)benzoate

HRID 1772071Notes

Reaction equation

HRID 1772071 reaction equation
Br[CH2:2][C:3]1[CH:13]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:11]=[CH:10][C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6].[NH2:18][C:19]1[C:20]([CH3:48])=[C:21]([C:25]2[N:26]=[C:27]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[O:41])=[CH:36][CH:35]=3)[C:28](=[O:32])[N:29]([CH3:31])[CH:30]=2)[CH:22]=[CH:23][CH:24]=1.C(N(C(C)C)CC)(C)C.C([O-])([O-])=O.[Na+].[Na+]>CCO>[C:14]([C:12]1[CH:11]=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:3]([CH2:2][NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]3[N:26]=[C:27]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([C:40]([N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[O:41])=[CH:38][CH:39]=4)[C:28](=[O:32])[N:29]([CH3:31])[CH:30]=3)[C:20]=2[CH3:48])[CH:13]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 469423835-(3-Amino-2-methylphenyl)-1-methyl-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazin-2-oneHCID 66610253Ethyl 2-(bromomethyl)-4-tert-butylbenzoate

Product 1

HCID 66610366Ethyl 4-tert-Butyl-2-((2-methyl-3-(4-methyl-6-(4-(morpholine-4-carbonyl)phenyl amino)-5-oxo-4,5-dihydropyrazin-2yl)phenylamino)methyl)benzoate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with bromide 101c (120 mg, 0.4 mmol), aniline 101g (168 mg, 0.4 mmol), diisopropyethylamine (0.08 mL, 0.48 mmol) in EtOH (3 mL). After the mixture was stirred at 100° C. for 16 h, aqueous Na2CO3 (5 mL) was added. The aqueous phase was extracted with EtOAc (2×5 mL), and the combined organic extracts were washed with brine (5 mL), dried with Na2SO4 and concentrated. The residue was chromatographed with (gradient, 50%-100% EtOAc/hexanes) to afford 100 mg (42%) of 101h.

Workup

  1. customA 48-mL sealed tube
  2. customequipped with a magnetic stirring bar
  3. extractionThe aqueous phase was extracted with EtOAc (2×5 mL)
  4. washthe combined organic extracts were washed with brine (5 mL)
  5. dry with materialdried with Na2SO4
  6. concentrationconcentrated
  7. customThe residue was chromatographed with (gradient, 50%-100% EtOAc/hexanes)
  8. customto afford 100 mg (42%) of 101h.

Sources & evidence

ORD record
ord-9daf8885401042fe8997172bab40218f
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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