Morpholine → HCID 136388375, compound

HRID 354183Notes

Reaction equation

HRID 354183 reaction equation
[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9]([C:28](=[O:31])[CH2:29]Br)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(N(CC)CC)C>ClCCl>[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9]([C:28](=[O:31])[CH2:29][N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 135730596HCID 135730596, compound

Product 1

HCID 136388375HCID 136388375, compoundYield 33.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triphenylphosphine (110 mg, 0.42 mmol) in dichloromethane (1 mL) was added slowly to an ice cooled solution of 5-(2-butoxy-5-glycoloyl-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one (Example 33) (150 mg, 0.35 mmol) and carbon tetrabromide (140 mg, 0.42 mmol) in dichloromethane (3 mL). The solution was allowed to warm to room temperature. After 2 h further carbon tetrabromide (25 mg, 0.075 mmol) and triphenylphosphine were added and stirring continued for 2 h. Concentration and purification of the product by flash column chromatography (gradient elution with ethyl acetate/pentane (10:90-70:30) gave 5-[2-butoxy-5-(2-bromoacetyl)-3-pyridinyl]-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one which was used without any further purification (slight contamination with triphenylphosphine oxide). 5-[2-Butoxy-5-(2-bromoacetyl)-3-pyridinyl]-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (205 mg, 0.42 mmol) was dissolved in dichloromethane and the solution cooled to 0° C. Morpholine (54 mg, 0.62 mmol) and triethylamine (84 mg, 0.83 mmol) were added and the mixture was allowed to warm to room temperature and stirred for 2 h. The solvent was evaporated and the residue dissolved in ethyl acetate, washed with water (twice), saturated sodium bicarbonate (twice) and brine, dried (MgSO4) and concentrated. Purification by flash column chromatography (gradient elution 20% ethyl acetate/pentane:100% ethyl acetate:3% methanol/methyl acetate) gave 70 mg product.

Workup

  1. customwas used without any further purification (slight contamination with triphenylphosphine oxide)
  2. temperatureto warm to room temperature
  3. customThe solvent was evaporated
  4. dissolutionthe residue dissolved in ethyl acetate
  5. washwashed with water (twice), saturated sodium bicarbonate (twice) and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customPurification
  9. washby flash column chromatography (gradient elution 20% ethyl acetate/pentane:100% ethyl acetate:3% methanol/methyl acetate)

Sources & evidence

ORD record
ord-86510076e75d4b478c096e124c27c851
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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