Triphenylphosphine → 2-(5-Amino-1-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-1H-pyrazol-3-yl)-2-methyl-propionitrile

HRID 2200050Notes

Reaction equation

HRID 2200050 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([OH:13])[CH:8]=2)[N:5]=[C:4]([C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH:3]=1.[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:25][CH2:26][CH2:27]O.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>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:27][CH2:26][O:25][CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][O:19]3)[CH:8]=2)[N:5]=[C:4]([C:14]([CH3:18])([CH3:17])[C:15]#[N:16])[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 41668332-(Oxan-2-yloxy)ethan-1-olHCID 1177292592-[5-Amino-1-(3-hydroxy-phenyl)-1H-pyrazol-3-yl]-2-methyl-propionitrile

Product 1

HCID 1177287572-(5-Amino-1-{3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-1H-pyrazol-3-yl)-2-methyl-propionitrileYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice cooled solution of Intermediate 20b (363 mg, 1.50 mmol), 2-(tetrahydro-2H-pyran-2-yloxy)ethanol (329 mg, 305 μL, 2.25 mmol) and triphenylphosphine (786 mg, 3.00 mmol) in anhydrous THF (10 mL) was added dropwise diisopropyl azodicarboxylate (606 mg, 590 μL), and the ice bath removed and stirring continued under an Ar atmosphere. After 3 h, a further 1.0 eq of diisopropyl azodicarboxylate was added and the reaction stirred overnight. The reaction mixture was then concentrated in vacuo and subjected to FCC, eluting with 5-50% EtOAc in cyclohexane. The isolated product was repurified using FCC, eluting with 2.5-7.5% Et2O in DCM, to afford the title compound as a yellow oil (317 mg, 57%). LCMS (Method 3): Rt 3.67 min, m/z 393.3 [M+Na].

Workup

  1. customthe ice bath removed
  2. stirringthe reaction stirred overnight
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. washeluting with 5-50% EtOAc in cyclohexane
  5. customThe isolated product was repurified
  6. washeluting with 2.5-7.5% Et2O in DCM

Sources & evidence

ORD record
ord-31d7a239deb448f9aa8ef7bd59a146b6
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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