Methanol → HCID 20607190, compound

HRID 431062Notes

Reaction equation

HRID 431062 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]=[C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[C:18]([Cl:24])[CH:17]=2)[C:11]([C:25](=[O:34])[NH:26][CH2:27][C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:10][N:9]=1.B(Br)(Br)Br.CO.C(=O)([O-])O.[Na+]>C(Cl)Cl.C(Cl)(Cl)Cl>[OH:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]=[C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([Cl:24])[CH:17]=2)[C:11]([C:25](=[O:34])[NH:26][CH2:27][C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)=[CH:10][N:9]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 9869929Avanafil

Product 1

HCID 20607190HCID 20607190, compoundYield 43.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-pyrimidylmethyl)carbamoyl]-pyrimidine (307 mg) obtained in Example 1-(5) in methylene chloride (6 ml) is added dropwise boron bromide (300 μl) under ice-cooling. The reaction mixture is stirred at 0° C. for 4 hours, and thereto is added methanol, and then a saturated aqueous sodium hydrogen carbonate solution under ice-cooling. The mixture is extracted with a mixture of ethyl acetate and tetrahydrofuran, and the organic layer is washed successively with water and brine. The mixture is dried over sodium sulfate, and concentrated under reduced pressure to give a slightly brown amorphous (227 mg). The resultant is suspended in chloroform, and the resulting insoluble materials are removed by filtration. The filtrate is subjected to silica gel column chromatography, and further purified by NH-silica gel column chromatography to give (S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-hydroxybenzylamino)-5-[N-(2-pyrimidylmethyl)carbamoyl]pyrimidine (129 mg) as a colorless foam, MS (m/z): 470 (MH+), IR (Nujol): 3279, 1632, 1593, 1569, 1518, 1463 cm−1.

Workup

  1. temperaturecooling
  2. extractionThe mixture is extracted with a mixture of ethyl acetate and tetrahydrofuran
  3. washthe organic layer is washed successively with water and brine
  4. dry with materialThe mixture is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a slightly brown amorphous (227 mg)
  7. customthe resulting insoluble materials are removed by filtration
  8. customfurther purified by NH-silica gel column chromatography

Sources & evidence

ORD record
ord-2cb274111f36427986d70bd36dbed220
Source dataset
uspto-grants-2003_12
Patent number
US06656935B2

Reaction notes

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