Triphenylphosphine → HCID 58739255, compound

HRID 720674Notes

Reaction equation

HRID 720674 reaction equation
[CH3:1][C:2]1[C:6]([C:7]([OH:9])=O)=[C:5]([CH3:10])[O:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClN1C(=O)CCC1=O.[CH:38]1([CH2:41][N:42]2[C:50]3[N:49]=[C:48]([CH2:51][C:52]4[CH:57]=[CH:56][C:55]([NH:58][CH3:59])=[CH:54][CH:53]=4)[NH:47][C:46]=3[C:45](=[O:60])[N:44]([CH2:61][C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=3[F:68])[C:43]2=[O:69])[CH2:40][CH2:39]1>ClCCl>[CH:38]1([CH2:41][N:42]2[C:50]3[N:49]=[C:48]([CH2:51][C:52]4[CH:53]=[CH:54][C:55]([N:58]([CH3:59])[C:7]([C:6]5[C:2]([CH3:1])=[N:3][O:4][C:5]=5[CH3:10])=[O:9])=[CH:56][CH:57]=4)[NH:47][C:46]=3[C:45](=[O:60])[N:44]([CH2:61][C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=3[F:68])[C:43]2=[O:69])[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 756363,5-Dimethylisoxazole-4-carboxylic acidHCID 218916913-Cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione

Product 1

HCID 58739255HCID 58739255, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 3,5-dimethyl-isoxazole-4-carboxylic acid (8.1 mg, 0.057 mmol) in dichloromethane (1.5 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. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 2:98 methanol/dichloromethane) afforded 3,5-dimethyl-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 (7.4 mg, 23.2%) as an off-white solid: EI-HRMS m/e calcd for C30H29N6O4F (M+) 556.2234, found 556.2229.

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

Sources & evidence

ORD record
ord-752df9d2960d48998632cd1a725a259c
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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