Sodium Carbonate → HCID 67995209, compound

HRID 2361418Notes

Reaction equation

HRID 2361418 reaction equation
Cl[C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][C:10]([C:15]([O:17][CH3:18])=[O:16])=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:19]#[N:20])=[CH:4][N:3]=1.[F:21][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[N:30]=[CH:29][N:28]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34](B3OC(C)(C)C(C)(C)O3)[C:33]=1[CH3:47])[C:27]2=[O:48].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[CH3:18][O:17][C:15]([C:10]1[CH:11]=[CH:12][C:13]2[C:14]3[C:2]([C:34]4[CH:35]=[CH:36][CH:37]=[C:32]([N:28]5[C:27](=[O:48])[C:26]6[C:31](=[C:22]([F:21])[CH:23]=[CH:24][CH:25]=6)[N:30]=[CH:29]5)[C:33]=4[CH3:47])=[N:3][CH:4]=[C:5]([C:19]#[N:20])[C:6]=3[NH:7][C:8]=2[CH:9]=1)=[O:16]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 67994969HCID 67994969, compoundHCID 86681528HCID 86681528, compound

Product 1

HCID 67995209HCID 67995209, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A stirred mixture of methyl 1-chloro-4-cyano-5H-pyrido[4,3-b]indole-7-carboxylate (0.285 g, 0.998 mmol), 8-fluoro-3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazolin-4(3H)-one (0.379 g, 0.998 mmol), Tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.050 mmol) and Sodium carbonate[2M aqueous] (0.499 mL, 0.998 mmol) in Dioxane (2 mL) was heated at 110° C. for 16 hours overnight. LC-MS showed complete conversion to the desired product mass plus residual starting material[boronic ester] and a byproduct. The reaction mixture was concentrated. The residue was taken up in 10 ml DMF, stirred and filtered. The filtrate was concentrated; the residue triturated with methanol and filtered. The solid residue labeled 89040-079-04 was dried overnight. LC-MS showed the solid residue to be the desired product Methyl-4-cyano-1-(3-(8-fluoro-4-oxoquinazolin-3(4H)-yl)-2-methylphenyl)-5H-pyrido[4,3-b]indole-7-carboxylate as a tan solid [0.172 g, 0.342 mmol, 34% yield]. The product had an HPLC Retention Time=3.510 min [mixture of rotamers][4 min grad, 10% MeOH/water to 90% MeOH/water, 0.1% TFA, YMC COMBISCREEN® ODS-A, 4.6×50 mm, 220 nM]; LC/MS+1 504.3.

Sources & evidence

ORD record
ord-beb81d9fc54b4a81a2b67576b35b4c0d
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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