Sodium Carbonate → HCID 66604798, compound

HRID 2410875Notes

Reaction equation

HRID 2410875 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][O:22][CH2:21][CH2:20]3)=[O:18])=[CH:13][CH:12]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH2:25](B1OC(C)(C)C(C)(C)O1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=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.CO.C1(C)C=CC=CC=1>[CH2:25]([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][O:22][CH2:21][CH2:20]3)=[O:18])=[CH:13][CH:12]=2)=[C:6]([CH:9]=1)[C:7]#[N:8])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 10340Sodium Carbonate2×HCID 38649642-Benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane2×HCID 66604956HCID 66604956, compound

Product 1

HCID 66604798HCID 66604798, compoundYield 41.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 887MethanolSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
110 °C

Procedure

A 5 ml microwave vial was loaded with 5-bromo-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile (125 mg, 0.259 mmol, Example 160A), 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (79 mg, 0.362 mmol) and Pd(Ph3P)4 (15 mg, 0.013 mmol). Toluene (1 mL), MeOH (0.500 mL) and a 2 molar solution of Na2CO3 (0.324 mL, 0.647 mmol) were added, the flask flushed with nitrogen, sealed and heat to 110° C. for 4 hours. LCMS after 4 hours showed product and starting material (1:2.5 ratio) (product m/e−=396, consistent with [M−H]−). Additional 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (400 mg, 1.834 mmol) and Pd(Ph3P)4 (30 mg, 0.026 mmol), Toluene (1 mL), MeOH (0.500 mL) and a 2 molar solution of Na2CO3 (0.324 mL, 0.647 mmol) were added. The flask was flushed with nitrogen, sealed and heated to 110° C. for additional 8 hours. The reaction mixture was poured into a separating funnel loaded with water and dichloromethane. The layers were separated and the aqueous layer extracted one more time with dichloromethane. The combined organic layers were washed with brine and dried over MgSO4, filtered and concentrated in vacuum. The crude product was purified by column chromatography on silica, using a gradient from 100% CH2Cl2 to 50% CH2Cl2+50 EtOAc. Product containing fraction were combined and evaporated to dryness to give 42.3 mg 5-benzyl-2-(4-(morpholine-4-carbonyl)phenylamino)benzonitrile. (estimated purity 76%). The material was used without further purification. MS (ESI) m/e−=396, m/e+=398 consistent with [M−H]− and [M+H]+.

Workup

  1. customthe flask flushed with nitrogen
  2. customsealed
  3. customThe flask was flushed with nitrogen
  4. customsealed
  5. temperatureheated to 110° C. for additional 8 hours
  6. additionThe reaction mixture was poured into a separating funnel
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted one more time with dichloromethane
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuum
  13. customThe crude product was purified by column chromatography on silica
  14. additionProduct containing fraction
  15. customevaporated to dryness

Sources & evidence

ORD record
ord-267b8bb4760a459287655dd5e5906505
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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