Ammonia → HCID 178463388, compound

HRID 1620243Notes

Reaction equation

HRID 1620243 reaction equation
C([O:4][C:5]1[N:6]=[C:7]([CH2:19][N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH3:16])=[C:10]([O:17][CH3:18])[CH:9]=2)(=O)C.N.[Li+].[OH-].Cl[CH2:35][C:36]1[C:37]([NH:48][CH2:49][CH3:50])=[N:38][C:39]2[C:44]([CH:45]=1)=[CH:43][C:42]([O:46][CH3:47])=[CH:41][CH:40]=2>C(Cl)Cl.CO>[CH2:49]([NH:48][C:37]1[C:36]([CH2:35][C:14]2[C:13]3[C:8](=[CH:9][C:10]([O:17][CH3:18])=[C:11]([O:15][CH3:16])[CH:12]=3)[C:7]([CH2:19][N:20]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])=[N:6][C:5]=2[OH:4])=[CH:45][C:44]2[C:39](=[CH:40][CH:41]=[C:42]([O:46][CH3:47])[CH:43]=2)[N:38]=1)[CH3:50]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 3939Lithium HydroxideHCID 681822081-((1,3-Dioxoisoindolin-2-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate2×HCID 681822213-(chloromethyl)-N-ethyl-6-methoxyquinolin-2-amine

Product 1

HCID 178463388HCID 178463388, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-((1,3-dioxoisoindolin-2-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate SIL 32166 (297 mg, 0.73 mmol) in dry CH2Cl2 (9 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer was added a 7 N NH3 solution in MeOH (1 mL) and the reaction mixture was stirred for 4 h at RT then concentrated to dryness at 40° C. under vacuum. The solid was taken up in THF (7 mL) and transferred in a 20 mL microwave vial equipped with a magnetic stirrer before addition of a 2 N aq. LiOH solution (0.37 mL, 0.74 mmol) and 3-(chloromethyl)-N-ethyl-6-methoxyquinolin-2-amine SLA 28166 free base (240 mg, 0.96 mmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (80 mL) and the organic solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 97:3) followed by a second purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100) gave 2-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)isoindoline-1,3-dione CCH 42006-1 as a yellow oil (75 mg, 32%).

Workup

  1. concentrationthen concentrated to dryness at 40° C. under vacuum
  2. stirringthe mixture was stirred at 150° C. for 1.5 h under microwave irradiation
  3. temperatureAfter cooling to RT
  4. washMeOH=9:1 (80 mL) and the organic solution was washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at 40° C. under vacuum
  8. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 97:3)
  9. customfollowed by a second purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-ef0a628f55a746828da6f16a6899debb
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

Loading…