1,2-Dimethoxyethane → 10-[3-(5-{[5-(4-Ethylpiperazin-1-yl)pyridine-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(acetoxymethyl)phenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one

HRID 1919038Notes

Reaction equation

HRID 1919038 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:23][CH2:22][N:21]3[C:14](=[CH:15][C:16]4[CH2:17][C:18]([CH3:25])([CH3:24])[CH2:19][C:20]=43)[C:13]2=[O:26])=[CH:10][C:9]([F:27])=[CH:8][C:7]=1Br)(=[O:3])[CH3:2].[CH2:29]([N:31]1[CH2:36][CH2:35][N:34]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44]3[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48](B4OC(C)(C)C(C)(C)O4)[CH:49]=3)=[N:41][CH:42]=2)[CH2:33][CH2:32]1)[CH3:30].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(Cl)Cl>[CH2:29]([N:31]1[CH2:36][CH2:35][N:34]([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44]3[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48]([C:7]4[C:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])=[C:11]([N:12]5[CH2:23][CH2:22][N:21]6[C:14](=[CH:15][C:16]7[CH2:17][C:18]([CH3:25])([CH3:24])[CH2:19][C:20]=76)[C:13]5=[O:26])[CH:10]=[C:9]([F:27])[CH:8]=4)[CH:49]=3)=[N:41][CH:42]=2)[CH2:33][CH2:32]1)[CH3:30]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580439513-(5-(4-Ethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 670163042-Bromo-4-fluoro-6-(9-oxo-4,4-dimethyl-1,10diazatricyclo[6.4.0.02,6]-dodeca-2(6),7-dien-10-yl)benzyl Acetate

Product 1

HCID 6820843810-[3-(5-{[5-(4-Ethylpiperazin-1-yl)pyridine-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(acetoxymethyl)phenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a microwave tube equipped with a stirring bar, 189a (381.9 mg, 0.850 mmol), 3-(5-(4-ethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (201a) (560 mg, 1.275 mmol), Pd(PPh3)4 (49.1 mg, 0.043 mmol), Na2CO3 aqueous solution (1.0 N, 2.81 mL, 2.81 mmol), 1,2-dimethoxy-ethane (4 mL) were added. The mixture was reacted in microwave at 130° C. for 10 min. methylene chloride (200 mL) was added and the resulting mixture was washed with water (30 mL×3), brine (30 mL×1), dried over MgSO4, filtered, and removed solvent in vacuo. Silica gel column chromatography (methanol:methylene chloride=5:95) gave 238a.

Workup

  1. customTo a microwave tube equipped with a stirring bar
  2. additionwas added
  3. washthe resulting mixture was washed with water (30 mL×3), brine (30 mL×1)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customremoved solvent in vacuo

Sources & evidence

ORD record
ord-0db28ad1eb4842d4a708088802a09c73
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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