Triphenylphosphine → 3-tert-butyl-1-(3-(2-(tetrahydro-2H-pyran-2-yloxy)ethoxy)phenyl)-1H-pyrazol-5-amine

HRID 630862Notes

Reaction equation

HRID 630862 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2O)[N:5]=[C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]1[O:43][CH2:44][CH2:45][OH:46].N(C(OCC)=O)=NC(OCC)=O>C1COCC1.O>[C:14]([C:4]1[CH:3]=[C:2]([NH2:1])[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:46][CH2:45][CH2:44][O:43][CH:38]3[CH2:39][CH2:40][CH2:41][CH2:42][O:37]3)[CH:8]=2)[N:5]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 41668332-(Oxan-2-yloxy)ethan-1-olHCID 587052255-Amino-3-tert-butyl-pyrazol-1-yl-phenol

Product 1

HCID 579256593-tert-butyl-1-(3-(2-(tetrahydro-2H-pyran-2-yloxy)ethoxy)phenyl)-1H-pyrazol-5-amineYield 134.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of intermediate 95a (1.42 g, 6.15 mmol) and triphenyl phosphine (3.22 g, 12.29 mmol) in THF (50 mL), under an atmosphere of argon was treated with 2-(tetrahydro-pyran-2-yloxy)-ethanol (1.25 mL, 9.22 mmol), followed by the dropwise addition of diethyl azodicarboxylate (1.94 mL, 12.29 mmol). The reaction mixture was then stirred at RT for 1 h. Water (0.5 mL) was added and the mixture was concentrated in vacuo. The residue was taken up in EtOAc (8 mL) and cyclohexane was added until triphenylphosphine oxide had precipitated out of solution. This was filtered and the filtrate was concentrated in vacuo. The residue was purified by FCC, using 0-100% EtOAc in cyclohexane to afford the title compound as an orange/brown oil (2.98 g, >100%). LCMS (Method 3): Rt 3.20 min, m/z 360 [MH+].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additioncyclohexane was added until triphenylphosphine oxide
  3. customhad precipitated out of solution
  4. filtrationThis was filtered
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-5adc8802afe84ed5b463a4974060b1f3
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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