1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one → 10-[2-(Acetoxymethyl)-3-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one

HRID 1918937Notes

Reaction equation

HRID 1918937 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)=[CH:20][N:19]=2)[C:3]1=[O:31].[C:32]([O:35][CH2:36][C:37]1[C:42]([N:43]2[CH2:54][CH2:53][N:52]3[C:45](=[CH:46][C:47]4[CH2:48][C:49]([CH3:56])([CH3:55])[CH2:50][C:51]=43)[C:44]2=[O:57])=[CH:41][CH:40]=[CH:39][C:38]=1Br)(=[O:34])[CH3:33]>C([O-])([O-])=O.[Na+].[Na+].COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:32]([O:35][CH2:36][C:37]1[C:38]([C:6]2[CH:5]=[C:4]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)=[CH:20][N:19]=3)[C:3](=[O:31])[N:2]([CH3:1])[CH:7]=2)=[CH:39][CH:40]=[CH:41][C:42]=1[N:43]1[CH2:54][CH2:53][N:52]2[C:45](=[CH:46][C:47]3[CH2:48][C:49]([CH3:56])([CH3:55])[CH2:50][C:51]=32)[C:44]1=[O:57])(=[O:34])[CH3:33]

Participants

6

Reactant 2

HCID 580437641-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 680968852-Bromo-6-[7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl]benzyl Acetate

Product 1

HCID 8666124510-[2-(Acetoxymethyl)-3-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-oneYield 26%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
125 °C

Procedure

In a 10-mL glass vessel equipped with a magnetic stirring bar were placed 1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one 197e (210 mg, 0.49 mmol), 10-[2-(acetoxymethyl)-3-bromophenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 167f (143 mg, 0.33 mmol), Pd(PPh3)4 (30 mg, 0.0.26 mmol) in 2 N Na2CO3 (2 mL) and 1,2-dimethoxyethane (5 mL). The vessel was sealed with a septum and placed into the microwave cavity. After the reaction mixture was stirred at 125° C. for 7 min., it was purified by flash chromatography (dichloromethane:methanol, 85:15) to give 26% (50 mg) of 173a as a solid.

Workup

  1. customIn a 10-mL glass vessel equipped with a magnetic stirring bar
  2. customThe vessel was sealed with a septum
  3. customit was purified by flash chromatography (dichloromethane:methanol, 85:15)

Sources & evidence

ORD record
ord-a65ea5da3f314af98a68e0c89ab69f29
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…