Methyl 6-amino-5-chloronicotinate → Methyl 6-amino-5-chloronicotinate

HRID 872308Notes

Reaction equation

HRID 872308 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH2:11])=[N:6][CH:5]=1.[C:13]([O:17][C:18](=[O:40])[NH:19][C:20]1([C:24]2[CH:29]=[CH:28][C:27]([C:30](=O)[CH:31](Br)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:26][CH:25]=2)[CH2:23][CH2:22][CH2:21]1)([CH3:16])([CH3:15])[CH3:14]>C(O)(C)C.C(Cl)Cl.O>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]2[N:6]([C:31]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[C:30]([C:27]3[CH:26]=[CH:25][C:24]([C:20]4([NH:19][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:40])[CH2:23][CH2:22][CH2:21]4)=[CH:29][CH:28]=3)[N:11]=2)[CH:5]=1)=[O:12].[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH2:11])=[N:6][CH:5]=1

Participants

7

Reactant 2

HCID 45594319Methyl 6-amino-5-chloronicotinateHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 2

HCID 45594319Methyl 6-amino-5-chloronicotinateHCID 666654742-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-8-chloro-3-phenyl-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-amino-5-chloronicotinic acid methyl ester (0.588 g, 3.15 mmol), {1-[4-(2-bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [Int-1-A] (2.00 g, 70% purity by UPLC-MS, 3.15 mmol) and powdered activated 3 Å molecular sieves in isopropanol (9.7 mL) was heated at reflux for 20 hours. On cooling, the mixture was diluted with DCM and water, filtered through Celite and the organic extract washed with brine, dried and concentrated in vacuo. Purification was achieved by chromatography on silica gel (gradient elution: hexane-hexane/ethyl acetate 1:1) to give the title compound contaminated with 6-amino-5-chloronicotinic acid methyl ester. Further purification was achieved by acid extraction of a solution of the crude product in ethyl acetate with dilute aqueous hydrochloric acid (1 M). The organic extract was washed with brine, dried and concentrated in vacuo to give the title compound;

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 20 hours
  3. temperatureOn cooling
  4. filtrationfiltered through Celite
  5. extractionthe organic extract
  6. washwashed with brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customPurification

Sources & evidence

ORD record
ord-ef580607d65340f7b466f50e75715fce
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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