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Sodium Carbonate → (S)-ethyl 2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate

HRID 518253
Notes
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Reaction equation

HRID 518253 reaction equation
NC1N=C(N[C@H]([C:11]2[N:12](C3C=CC=CC=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=CC=CC=3Cl)C)C(C#N)=CN=1.[NH2:31][C:32]1[N:37]=[C:36]([NH:38][C@H:39]([C:41]2[N:42]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:43](=[O:52])[C:44]3[C:49]([CH:50]=2)=[CH:48][CH:47]=[CH:46][C:45]=3Cl)[CH3:40])[C:35]([C:59]([O:61][CH2:62][CH3:63])=[O:60])=[CH:34][N:33]=1.B(O)O.[CH:67]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:31][C:32]1[N:37]=[C:36]([NH:38][C@H:39]([C:41]2[N:42]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:43](=[O:52])[C:44]3[C:49]([CH:50]=2)=[CH:48][CH:47]=[CH:46][C:45]=3[C:19]2[CH:20]=[CH:11][N:12]=[C:13]([O:22][CH3:67])[CH:14]=2)[CH3:40])[C:35]([C:59]([O:61][CH2:62][CH3:63])=[O:60])=[CH:34][N:33]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 67950671(S)-2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrileHCID 71275988(S)-ethyl 2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate

Product 1

HCID 71276087(S)-ethyl 2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

Compound 109 was prepared from compound 8 according to Method G. Compound 109 was then converted to compound 110 according to the following procedure: The mixture of (S)-ethyl 2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate (300 mg, 0.65 mmol) and 2-methoxypyridin-4-yl)boronic acid (149 mg, 0.98 mmol) in 1,4-dioxane:water (3:1, 12 mL) was degassed and backfilled with argon (three cycles). To this mixture, 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (121 mg, 0.26 mmol), palladium(II) acetate (29 mg, 0.13 mmol), and Na2CO3 (207 mg, 1.95 mmol) were added sequentially. The resulting mixture was degassed and backfilled with argon (three cycles), and then stirred at 120° C. for 3 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM) to afford the product 110, (S)—ethyl 2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate.

Workup

  1. customwas degassed
  2. customThe resulting mixture was degassed
  3. temperatureto cool to RT
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-46eca5275bda46f99b7b708a2963f50f
Source dataset
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09115141B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes