Triphenylphosphine → 5-tert-Butyl-2-{4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-ylamine

HRID 75590Notes

Reaction equation

HRID 75590 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:3]=1.[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26]O)[CH2:21][CH2:20]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(OCC)C>[C:14]([C:4]1[CH:3]=[C:2]([NH2:1])[N:6]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:26][CH2:25][N:22]3[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]3)=[CH:9][CH:8]=2)[N:5]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 595579504-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenol

Product 1

HCID 866866925-tert-Butyl-2-{4-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-ylamineYield 15.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 13b (1.15 g, 5.0 mmol), 2-(4-methyl-piperazin-1-yl)-ethanol (864 mg, 6.0 mmol), and triphenylphosphine (2.62 g, 10.0 mmol) in THF (10 mL), was added diisopropyl azodicarboxylate (2.0 g, 10.0 mmol) dropwise and stirred for 75 min. The mixture was diluted with diethyl ether (50 mL) and extracted with 10% aqueous citric acid soln (2×). The combined aqueous layers were basified with solid potassium carbonate until pH=9. The aqueous layer was then extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with brine, dried (NaSO4) and evaporated in vacuo. Purification by FCC using 0-12% [9:1 MeOH/880 ammonia] in DCM. The resulting product was crystallised (diethyl ether) to give the title compound (270 mg, 0.756 mmol, 15%). LCMS (Method 1): Rt 2.31, 1.72 min, m/z 358/359 [MH+].

Workup

  1. extractionextracted with 10% aqueous citric acid soln (2×)
  2. extractionThe aqueous layer was then extracted with ethyl acetate (3×)
  3. washThe combined ethyl acetate layers were washed with brine
  4. dry with materialdried (NaSO4)
  5. customevaporated in vacuo
  6. customPurification by FCC
  7. customThe resulting product was crystallised (diethyl ether)

Sources & evidence

ORD record
ord-dc7deccf057945488c466199af96cfc3
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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