Methanol → HCID 66599387, compound

HRID 2410707Notes

Reaction equation

HRID 2410707 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[O:18])=[CH:13][CH:12]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CO>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.C1(C)C=CC=CC=1>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:2]1[CH:3]=[CH:4][C:5]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[O:18])=[CH:15][CH:16]=2)=[C:6]([C:7]#[N:8])[CH:9]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 66599439HCID 66599439, compound

Product 1

HCID 66599387HCID 66599387, compoundYield 84.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

5-Bromo-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)benzonitrile (100 mg, 0.250 mmol), Pd(Ph3P)4 (14.47 mg, 0.013 mmol), 2-methoxyphenylboronic acid (53.3 mg, 0.351 mmol), aqueous Na2CO3 (0.28 mL, 0.560 mmol), MeOH (0.5 mL) and Toluene (1 mL) were combined in a 2 ml microwave vial, sealed, the vial flushed with nitrogen and heated to 105° C. for 5 hrs in an oil bath. The reaction was poured into a separating funnel loaded with dichloromethane and 0.1 N aq. KOH. The aqueous layer was extracted one more time with dichloromethane, the organic layers combined and washed once with brine, then dried over MgSO4, filtered and concentrated in vacuum. Purification by chromatography on silica Solvent A: 500 ml ethyl acetate+500 ml CH2Cl2+10 ml Et3N; Solvent B: 500 ml ethyl acetate+500 ml CH2Cl2+10 ml Et3N+100 ml MeOH, Gradient from 100% A to 100% B, product elutes at ˜25% Solvent B. Combine product containing fractions and evaporate volatiles. 90.1 mg 2′-methoxy-4-(4-(4-methylpiperazine-1-carbonyl)phenylamino)-biphenyl-3-carbonitrile were isolated as a colorless film. MS (ESI) m/z 427 (M+H). 1H NMR (CDCl3) δ ppm 7.74 (d, 1H, J=2.2), 7.60 (dd, 1H, J=8.9, 1.9), 7.42 (d, 2H, J=8.5), 7.34 (d, 1H, J=8.9), 7.32 (dt, 1H, J=1.5, ˜8, ˜8), 7.26 (dd, 1H, J=1.6, ˜8), 7.20 (d, 2H, J=8.2), 7.02 (t, 1H, J=7.5), 6.98 (d, 1H, J=8.2), 6.49 (s, 1H), 3.83 (s, 3H), 3.85-3.45 (b, 4H), 2.43 (bs, 4H), 2.32 (s, 3H).

Workup

  1. customsealed
  2. customthe vial flushed with nitrogen
  3. additionThe reaction was poured into a separating funnel
  4. extractionThe aqueous layer was extracted one more time with dichloromethane
  5. washwashed once with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuum
  9. customPurification by chromatography on silica Solvent A
  10. additionCombine product containing fractions
  11. customevaporate volatiles

Sources & evidence

ORD record
ord-3c7046a2028c404da7d7138db0e8cc28
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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