Methyl Acrylate → HCID 86702544, compound

HRID 877069Notes

Reaction equation

HRID 877069 reaction equation
[C:1]([O:5][C:6](=[O:38])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:31]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:30][N:21]4[N:22]=[C:23]5[C:28]([CH:27]=[CH:26][CH:25]=[C:24]5Br)=[C:20]4[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:39][O:40][C:41](=[O:44])[CH:42]=[CH2:43].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[Cl-].[NH4+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.O>[CH3:39][O:40][C:41](=[O:44])/[CH:42]=[CH:43]/[C:24]1[C:23]2[C:28](=[C:20]3[N:19]=[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:8]5([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:38])[CH2:11][CH2:10][CH2:9]5)=[CH:13][CH:14]=4)[C:31]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:30][N:21]3[N:22]=2)[CH:27]=[CH:26][CH:25]=1

Participants

9

Reactant 5

HCID 7294Methyl Acrylate2×HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 80271Tri-o-tolylphosphineHCID 86702541HCID 86702541, compound

Product 1

HCID 86702544HCID 86702544, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

200 mg (0.351 mmol) {1-[4-(7-Bromo-3-phenylpyrimido[1,2-b]indazol-2-yl)phenyl]-cyclobutyl}carbamic acid tert-butyl ester (intermediate example Int-2-1), 60.5 mg (0.7 mmol) acrylic acid methyl ester, 18.2 mg (0.06 mmol) tri-2-tolylphosphane and 7.9 mg (0.035 mmol) palladium(II) acetate were given in 2.47 mL degassed acetonitrile. After addition of 40.5 mg (0.4 mmol) triethylamine the reaction mixture was stirred in the microwave for one hour at 110° C. Due to an incomplete reaction additional acrylic acid methyl ester (30 mg) and catalyst (4 mg) were added and stirring was continued for two hours at 110° C. The reaction mixture was poured on a mixture of water (10 mL), saturated ammonium chloride (60 mL) and dichloromethane (150 mL). After vigorous stirring the organic phase was separated and the water phase was reextracted with dichloromethane (50 mL). The combined organic extracts were washed with brine and dried (sodium sulfate). After removal of the solvent the crude product (275 mg, >100%) was used in the next step without further purification.

Workup

  1. customdegassed acetonitrile
  2. stirringstirring
  3. waitwas continued for two hours at 110° C
  4. stirringAfter vigorous stirring the organic phase
  5. customwas separated
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (sodium sulfate)
  8. customAfter removal of the solvent the crude product (275 mg, >100%)
  9. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-66c8c35ec9dc4866901924fb71b283d9
Source dataset
uspto-grants-2015_03
Patent number
US08987286B2

Reaction notes

Loading…