Sodium Carbonate → 10-[5-Fluoro-2-(acetoxymethyl)-3-(1-methyl-5-{[5-(1-methylpyrrolidin-2-yl)pyridine-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 1919041Notes

Reaction equation

HRID 1919041 reaction equation
C(OCC1C(C2N=C(NC3C=CC(C4CCNCC4)=CC=3)C(=O)N(C)C=2)=CC=CC=1N1C(=O)C2SC3CCCCC=3C=2CC1)(=O)C.[C:47]([O:50][CH2:51][C:52]1[C:57]([N:58]2[CH2:69][CH2:68][N:67]3[C:60](=[CH:61][C:62]4[CH2:63][C:64]([CH3:71])([CH3:70])[CH2:65][C:66]=43)[C:59]2=[O:72])=[CH:56][C:55]([F:73])=[CH:54][C:53]=1B1OC(C)(C)C(C)(C)O1)(=[O:49])[CH3:48].Br[C:84]1[CH:85]=[C:86]([NH:92][C:93]2[CH:98]=[CH:97][C:96]([CH:99]3[CH2:103][CH2:102][CH2:101][N:100]3[CH3:104])=[CH:95][N:94]=2)[C:87](=[O:91])[N:88]([CH3:90])[CH:89]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl.CO.COCCOC>[F:73][C:55]1[CH:54]=[C:53]([C:84]2[CH:85]=[C:86]([NH:92][C:93]3[CH:98]=[CH:97][C:96]([CH:99]4[CH2:103][CH2:102][CH2:101][N:100]4[CH3:104])=[CH:95][N:94]=3)[C:87](=[O:91])[N:88]([CH3:90])[CH:89]=2)[C:52]([CH2:51][O:50][C:47](=[O:49])[CH3:48])=[C:57]([N:58]2[CH2:69][CH2:68][N:67]3[C:60](=[CH:61][C:62]4[CH2:63][C:64]([CH3:70])([CH3:71])[CH2:65][C:66]=43)[C:59]2=[O:72])[CH:56]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 580439935-Bromo-1-methyl-3-(5-(1-methylpyrrolidin-2-yl)pyridin-2-ylamino)pyridin-2(1H)-oneHCID 670162322-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 670162355-[2-(Acetoxymethyl)-3-(4-methyl-5-oxo-6-{[4-(piperidin-4-yl)phenyl]-amino}-4,5-dihydropyrazin-2-yl)phenyl]-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-6-one

Product 1

HCID 8671169410-[5-Fluoro-2-(acetoxymethyl)-3-(1-methyl-5-{[5-(1-methylpyrrolidin-2-yl)pyridine-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 67%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
130 °C

Procedure

Example 243a was synthesized using the same procedure as 121b, except using compound 230a (446 mg, 0.9 mmol), 5-bromo-1-methyl-3-(5-(1-methylpyrrolidin-2-yl)pyridin-2-ylamino)pyridin-2(1H)-one (229a) (281 mg, 0.8 mmol), 1M sodium carbonate solution (2.7 mL, 2.7 mmol), tetrakis(triphenylphosphine)-palladium(0) (47 mg, 0.040 mmol) and 1,2-dimethoxyethane (6.5 mL).The reaction mixture was heated at 130° C. for 15 minutes in the microwave reactor. Work-up and flash column chromato-graphy (silica, 9:1 methylene chloride/methanol) give a 67% yield (350 mg) of 243a as brown oil: MS (ESI+) m/z 653.1 (M+H).

Workup

  1. customExample 243a was synthesized

Sources & evidence

ORD record
ord-1fd33d0fd6b74d72832f28e62a0c64af
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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