Sodium Hydroxide → HCID 123151394, compound

HRID 711199Notes

Reaction equation

HRID 711199 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[C:12]([CH2:25][O:26][Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])=[N:13][N:14]([CH2:16][CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[CH:15]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[Cl:39][C:40]([Cl:47])([Cl:46])[CH2:41][O:42][C:43](Cl)=[O:44]>CCOC(C)=O.O>[Cl:39][C:40]([Cl:47])([Cl:46])[CH2:41][O:42][C:43](=[O:44])[NH:10][C:8]1[N:7]([C:11]2[C:12]([CH2:25][O:26][Si:27]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:29])[CH3:30])[CH:34]([CH3:36])[CH3:35])=[N:13][N:14]([CH2:16][CH2:17][O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[CH:15]=2)[N:6]=[C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])[CH:9]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformate3×HCID 1231623413-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-3'-triisopropylsilanyloxymethyl-1'H-[1,4']bipyrazolyl-5-ylamine

Product 1

HCID 123151394HCID 123151394, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of Intermediate 74f (0.44 g, 0.85 mmol) in EtOAc (5 mL) was added 1N aqueous NaOH solution (1.7 mL, 1.7 mmol) followed by 2,2,2-trichloroethylchloroformate (0.13 mL, 0.93 mmol). The reaction was stirred at RT for 4 h then treated with another portion of 2,2,2-trichloroethylchloroformate (35 μL, 0.25 mmol) and stirred over the weekend. The reaction was treated with another portion of 2,2,2-trichloroethylchloroformate (35 μL, 0.25 mmol) and stirred for 1 h then diluted with EtOAc and water and the layers were separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-4% MeOH in DCM, to give the title compound (0.47 g, 80%). 1H NMR (300 MHz, CDCl3): 0.96 (18H, d, J=6.8 Hz), 1.01-1.17 (3H, m), 1.25 (9H, s), 1.38-1.51 (4H, m), 1.54-1.75 (2H, m), 3.36-3.45 (1H, m), 3.58-3.68 (1H, m), 3.68-3.77 (1H, m), 3.97-4.07 (1H, m), 4.24 (2H, t, J=4.7 Hz), 4.51 (1H, t, J=3.2 Hz), 4.59 (2H, s), 4.69-4.73 (2H, m), 6.26 (1H, s), 7.63 (1H, s), 7.74 (1H, s).

Workup

  1. stirringstirred over the weekend
  2. stirringstirred for 1 h
  3. customthe layers were separated
  4. extractionThe aqueous layer was then extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution, and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-6263698f6be44201b019cca09b248713
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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