Sodium Carbonate → 10-[3-(5-{[5-(Azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-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 1919025Notes

Reaction equation

HRID 1919025 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].[N:83]1([CH2:87][C:88]2[N:92]([CH3:93])[N:91]=[C:90]([NH:94][C:95]3[C:96](=[O:103])[N:97]([CH3:102])[CH:98]=[C:99](Br)[CH:100]=3)[CH:89]=2)[CH2:86][CH2:85][CH2:84]1.C(=O)([O-])[O-].[Na+].[Na+]>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.CO.COCCOC>[N:83]1([CH2:87][C:88]2[N:92]([CH3:93])[N:91]=[C:90]([NH:94][C:95]3[C:96](=[O:103])[N:97]([CH3:102])[CH:98]=[C:99]([C:53]4[C:52]([CH2:51][O:50][C:47](=[O:49])[CH3:48])=[C:57]([N:58]5[CH2:69][CH2:68][N:67]6[C:60](=[CH:61][C:62]7[CH2:63][C:64]([CH3:70])([CH3:71])[CH2:65][C:66]=76)[C:59]5=[O:72])[CH:56]=[C:55]([F:73])[CH:54]=4)[CH:100]=3)[CH:89]=2)[CH2:84][CH2:85][CH2:86]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 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-oneHCID 670163313-(5-(Azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-ylamino)-5-bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 6701641710-[3-(5-{[5-(Azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-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-oneYield 43%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
130 °C

Procedure

Example 230b was synthesized using the same procedure as 121b, except using compound 230a (223 mg, 0.45 mmol), 3-(5-(azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-ylamino)-5-bromo-1-methylpyridin-2(1H)-one (200c) (160 mg, 0.45 mmol), 1M sodium carbonate solution (1.5 mL, 1.5 mmol), tetrakis(triphenylphosphine)palladium(0) (26 mg, 0.022 mmol) and 1,2-dimethoxyethane (4.5 mL).The reaction mixture was heated at 130° C. for 15 minutes in the microwave reactor. Work-up and flash column chromatography (silica, 9:1 methylene chloride/methanol) give a 43% yield (120 mg) of compound 230b as brown oil: MS (ESI+) m/z 643.1 (M+H).

Workup

  1. customExample 230b was synthesized

Sources & evidence

ORD record
ord-18ed48f90b454949b41c3b15bcd4f4be
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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