Sodium Carbonate → HCID 86712632, compound

HRID 1778962Notes

Reaction equation

HRID 1778962 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:22]1[N:27]=[C:26]([C:28]#[C:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:36][C:37]([O-:39])=[O:38])[C:25]([CH3:40])=[CH:24][N:23]=1.[CH3:41]C1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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]>[CH3:41][O:39][C:37](=[O:38])[CH2:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C:29]#[C:28][C:26]1[C:25]([CH3:40])=[CH:24][N:23]=[C:22]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[N:27]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylateHCID 86712633HCID 86712633, compound

Product 1

HCID 86712632HCID 86712632, compoundYield 81.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (K3) (0.845 g, 3.06 mmol), methyl 2-(2-((2-chloro-5-methylpyrimidin-4-ylethynyl)phenyl)acetate (K7) (0.460 g, 1.53 mmol), Pd2(dba)3 (0.070 g, 0.076 mmol), Xantphos (0.089 g, 0.15 mmol), and Na2CO3 (0.648 g, 6.12 mmol) in DME (16 mL) was degassed with nitrogen before heating under microwave irradiation for 30 minutes at 110° C., then a further 60 minutes at 110° C. An additional 0.1 equivalent of Pd2(dba)3 and 0.1 equivalent of Xantphos were added before the solution was degassed with nitrogen for 5 minutes and heated under microwave irradiation for 60 minutes at 110° C. The resulting mixture was filtered and the filtrate evaporated in vacuo to give a dark brown residue which was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% MeOH in EtOAc), to yield the title compound A7 as brown oil (66 mg, 8%); 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.53-7.46 (m, 2H), 7.44-7.28 (m, 4H), 6.94 (dd, J=7.2, 5.1 Hz, 2H), 3.96 (s, 2H), 3.70 (s, 3H), 3.58 (dd, J=11.4, 6.2 Hz, 4H), 3.11-3.04 (m, 4H), 2.33 (s, 3H), 1.49 (s, 9H). LC-MS-A: rt 6.409 min; m/z 542 [M+H]+.

Workup

  1. customwas degassed with nitrogen
  2. customa further 60 minutes
  3. customat 110° C
  4. customwas degassed with nitrogen for 5 minutes
  5. temperatureheated under microwave irradiation for 60 minutes at 110° C
  6. filtrationThe resulting mixture was filtered
  7. customthe filtrate evaporated in vacuo
  8. customto give a dark brown residue which
  9. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% MeOH in EtOAc)

Sources & evidence

ORD record
ord-85afbf9736f549489be3649b82458ce7
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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