Trimethylaluminum → HCID 59860337, compound

HRID 252142Notes

Reaction equation

HRID 252142 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@H:11]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])[CH2:10]2)[N:3]=1.[CH3:24][Al](C)C>O1CCCC1.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>[Cl:23][C:17]1[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=1[CH2:15][NH:14][C@H:11]1[CH2:12][CH2:13][N:9]([C:4]2[N:3]=[C:2]([CH3:24])[C:7]([F:8])=[CH:6][N:5]=2)[CH2:10]1

Participants

5

Reactant 2

HCID 16682925TrimethylaluminumHCID 86625141HCID 86625141, compound

Product 1

HCID 59860337HCID 59860337, compoundYield 60.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Dissolve (S)-[1-(4-chloro-5-fluoropyrimidin-2-yl)-pyrrolidin-3-yl]-(2,4-dichlorobenzyl)-amine (318 mg, 0.84 mmol) in dry tetrahydrofuran (7.5 mL) and add trimethylaluminium (510 μL, 1.01 mmol, 2 M in hexanes) and tetrakis(triphenylphosphine)palladium(0) (68 mg, 0.06 mmol). Stir at 70° C. overnight. Quench by addition of water and extract with chloroform. Combine the organic layers and wash with saturated aqueous sodium chloride, dry (magnesium sulfate), filter and chromatograph on silica gel. Dissolve the residue in methanol (2 mL) and deposit onto SCX cartridge, eluting with methanol, then 2 M ammonia in methanol. Concentrate the ammonia washing to give the title compound (180 mg, 60%). 1H NMR (400 MHz, MeOH-d4) δ 7.88 (1H, d, J=6.4 Hz), 7.43-7.54 (2H, m), 7.27-7.37 (1H, m), 3.84-3.96 (4H, m), 3.67-3.78 (1H, m), 3.55-3.64 (1H, m), 3.43-3.53 (1H, m), 2.41 (3H, s), 2.14-2.26 (1H, m), 1.89-2.00 (1H, m); MS (ES): m/z=355 [M+].

Workup

  1. customQuench by addition of water
  2. extractionextract with chloroform
  3. washwash with saturated aqueous sodium chloride
  4. dry with materialdry (magnesium sulfate)
  5. filtrationfilter
  6. dissolutionDissolve the residue in methanol (2 mL)
  7. washdeposit onto SCX cartridge, eluting with methanol
  8. concentrationConcentrate the ammonia washing

Sources & evidence

ORD record
ord-057ab66add7e41fd91f2965941406beb
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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