Tributylphosphine → HCID 67520472, compound

HRID 1926051Notes

Reaction equation

HRID 1926051 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:20](=[CH:24][N:25]([CH2:27][CH2:28][CH2:29]O)[N:26]=3)[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH3:31][S:32]([CH2:35][CH2:36][NH:37][S:38]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[N+:47]([O-:49])=[O:48])(=[O:40])=[O:39])(=[O:34])=[O:33].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:19]3[C:20](=[CH:24][N:25]([CH2:27][CH2:28][CH2:29][N:37]([CH2:36][CH2:35][S:32]([CH3:31])(=[O:33])=[O:34])[S:38]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[N+:47]([O-:49])=[O:48])(=[O:39])=[O:40])[N:26]=3)[N:21]=[CH:22][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

8

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 57597272HCID 57597272, compoundHCID 67521417HCID 67521417, compound

Product 1

HCID 67520472HCID 67520472, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]propanol (50 mg), N-[2-(methylsulfonyl)ethyl]-2-nitrobenzenesulfonamide (47 mg), 1,1′-(azodicarbonyl)dipiperidine (59 mg) and tributylphosphine (47 mg) in tetrahydrofuran (2 mL) was stirred at room temperature for 4 hrs. After the completion of the reaction, water was added to the reaction mixture and the mixture was diluted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol=4/1→1/4) to give N-{3-[7-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-2H-pyrazolo[4,3-d]pyrimidin-2-yl]propyl}-N-[2-(methylsulfonyl)ethyl]-2-nitrobenzenesulfonamide. To a solution of this compound in tetrahydrofuran (2 mL) were added 2-mercaptoethanol (12 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (23 mg), and the mixture was stirred at room temperature for 3 hrs. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=10/1) to give the title compound (34 mg) as a white solid.

Workup

  1. additionwas added to the reaction mixture
  2. washwashed with saturated brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol=4/1→1/4)

Sources & evidence

ORD record
ord-c0e8487df7c04f2bbddb2c3e70abab1c
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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