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

HRID 572060Notes

Reaction equation

HRID 572060 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[NH2:15][C:16]1[N:20]([C:21]2[CH:22]=[C:23]([OH:27])[CH:24]=[CH:25][CH:26]=2)[N:19]=[C:18]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:17]=1.[O:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[O:38][CH2:39][CH2:40]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:28]([C:18]1[CH:17]=[C:16]([NH2:15])[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:40][CH2:39][O:38][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37][O:32]3)[CH:22]=2)[N:19]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 41668332-(Oxan-2-yloxy)ethan-1-olHCID 5363146Diisopropyl azodicarboxylateHCID 595579663-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)phenol

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIAD (847 μL, 4.32 mmol) was added slowly to a solution of 3-(5-amino-3-tert-butyl-1H-pyrazol-1-yl)phenol (for reference procedure see US 2006/35922, which is incorporated herein by reference in its entirety; 500 mg, 2.16 mmol), 2-(tetrahydro-pyran-2-yloxy)-ethanol (439 μL, 3.25 mmol), and triphenylphosphine (1.13 g, 4.32 mmol) in THF (10.0 mL) and stirred for 72 h. The reaction mixture was partitioned between EtOAc (75 mL) and H2O (75 mL), and the aqueous layer extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered and evaporated in vacuo. Purification by FCC, using 5-60% EtOAc in cyclohexane, gave semi-pure title compound (1.26 g). This was used in the next reaction without further purification. LCMS (Method 4): Rt 2.77, m/z 360 [MH+].

Workup

  1. customThe reaction mixture was partitioned between EtOAc (75 mL) and H2O (75 mL)
  2. extractionthe aqueous layer extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customPurification by FCC

Sources & evidence

ORD record
ord-0e408a2c1d38407ebf4ebda707399290
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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