Water → HCID 24958530, compound

HRID 1091553Notes

Reaction equation

HRID 1091553 reaction equation
[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([C:23](=[O:26])[NH:24][CH3:25])=[CH:19][C:18]=4[O:27][CH3:28])[N:12]=[CH:11][C:10]=3[N:9]3[CH:29]=[N:30][C:31](C(OCC=C)=O)=[C:8]3[C@H:7]2[CH2:38][CH3:39])[CH2:5][CH2:4][CH2:3][CH2:2]1.O>C(#N)C1C=CC=CC=1.C1(C)C=CC=CC=1.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>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([C:23]([NH:24][CH3:25])=[O:26])=[CH:19][C:18]=4[O:27][CH3:28])[N:12]=[CH:11][C:10]=3[N:9]3[CH:29]=[N:30][CH:31]=[C:8]3[C@H:7]2[CH2:38][CH3:39])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 962WaterHCID 59286706HCID 59286706, compound

Product 1

HCID 24958530HCID 24958530, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 7505BenzonitrileSolvent

Conditions

Temperature
155 °C

Procedure

A mixture of (R)-allyl 5-cyclopentyl-6-ethyl-3-(2-methoxy-4-(methylcarbamoyl)phenylamino)-5,6-dihydroimidazo[1,5-f]pteridine-7-carboxylate 1-3 (37 mg, 0.07 mmol) and tetrakis(triphenylphosphine)palladium(0) (7 mg) in benzonitrile (0.5 ml) and toluene saturated with water (0.5 ml) was heated under microwave irradiation at 155° C. for 1 hour. The mixture was cooled down to room temperature and evaporated to dryness. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, concentrated in vacuo and partitioned between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic phase was dried over magnesium sulphate and concentrated in vacuo to afford the title compound as a white solid (3.7 mg, 12% yield); 1H NMR (CDCl3) 0.73-0.85 (3H, m), 1.50-2.20 (10H, m), 3.00, 3.02 (3H, 2×s), 3.95, 3.96 (3H, 2×s), 4.50-4.65 (1H, m), 4.66-4.75 (1H, m), 6.10-6.24 (1H, m), 6.85-6.94 (1H, m), 7.21-7.30 (1H, m), 7.40-7.49 (1H, m), 7.68-7.75 (1H, m), 7.89-7.97 (1H, m), 8.20-8.28 (1H, m), 8.48-8.55 (1H, m); LC/MS M+1 (obs.) 448.61, LC/MS M-1 (obs.) 446.72.

Workup

  1. temperatureThe mixture was cooled down to room temperature
  2. customevaporated to dryness
  3. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  4. customThe fractions were collected
  5. concentrationconcentrated in vacuo
  6. custompartitioned between ethyl acetate
  7. dry with materialThe organic phase was dried over magnesium sulphate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a48386d77fe445a1ae497cbe0f9fcc71
Source dataset
uspto-grants-2012_03
Patent number
US08129387B2

Reaction notes

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