Triphenylphosphine → HCID 69663688, compound

HRID 720673Notes

Reaction equation

HRID 720673 reaction equation
[CH3:1][C:2]1[C:6]([C:7]([OH:9])=O)=[CH:5][O:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClN1C(=O)CCC1=O.[CH:37]1([CH2:40][N:41]2[C:49]3[N:48]=[C:47]([CH2:50][C:51]4[CH:56]=[CH:55][C:54]([NH:57][CH3:58])=[CH:53][CH:52]=4)[NH:46][C:45]=3[C:44](=[O:59])[N:43]([CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[F:67])[C:42]2=[O:68])[CH2:39][CH2:38]1>ClCCl>[CH:37]1([CH2:40][N:41]2[C:49]3[N:48]=[C:47]([CH2:50][C:51]4[CH:52]=[CH:53][C:54]([N:57]([CH3:58])[C:7]([C:6]5[C:2]([CH3:1])=[N:3][O:4][CH:5]=5)=[O:9])=[CH:55][CH:56]=4)[NH:46][C:45]=3[C:44](=[O:59])[N:43]([CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[F:67])[C:42]2=[O:68])[CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 218916913-Cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione

Product 1

HCID 69663688HCID 69663688, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 3-methyl-isoxazole-4-carboxylic acid (7.3 mg, 0.057 mmol) in dichloromethane (1.0 mL) cooled to 0° C. was treated with triphenylphosphine (17 mg, 0.063 mmol), and N-chlorosuccinimide (10 mg, 0.074 mmol). This mixture was stirred at 0° C. for 15 min and at 25° C. for 20 min. At this time, the reaction was treated with 3-cyclopropylmethyl-1-(2-fluoro-benzyl)-8-(4-methylamino-benzyl)-3,7-dihydro-purine-2,6-dione (50 mg, 0.11 mmol). The reaction was then stirred at 25° C. for 18 h. At this time, the reaction was diluted with dichloromethane (50 mL) and was washed with a saturated aqueous sodium bicarbonate solution (1×10 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The aqueous layer was re-extracted with dichloromethane (1×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford 3-methyl-isoxazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (6.8 mg, 21.8%) as an off-white solid: EI-HRMS m/e calcd for C29H27N6O4 (M+) 542.2078, found 542.2077.

Workup

  1. stirringThe reaction was then stirred at 25° C. for 18 h
  2. washwas washed with a saturated aqueous sodium bicarbonate solution (1×10 mL)
  3. dry with materialThe organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min)
  7. concentrationconcentrated in vacuo
  8. additionThe resulting residue was diluted with dichloromethane (100 mL)
  9. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
  10. extractionThe aqueous layer was re-extracted with dichloromethane (1×50 mL)
  11. dry with materialThe combined organics were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe resulting solid was dried in vacuo for 24 h

Sources & evidence

ORD record
ord-aacdaed9e97c416588f64e15859dae33
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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