Diisopropylethylamine → {5-tert-Butyl-2-[2-(2-morpholin-4-yl-ethyl)-2H-indazol-6-yl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 75611Notes

Reaction equation

HRID 75611 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH2:27])[N:8]([C:10]2[CH:11]=[CH:12][C:13]3[C:17]([CH:18]=2)=[N:16][N:15]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:14]=3)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[Cl:37][C:38]([Cl:45])([Cl:44])[CH2:39][O:40][C:41](Cl)=[O:42]>C1COCC1>[Cl:37][C:38]([Cl:45])([Cl:44])[CH2:39][O:40][C:41](=[O:42])[NH:27][C:7]1[N:8]([C:10]2[CH:11]=[CH:12][C:13]3[C:17]([CH:18]=2)=[N:16][N:15]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:14]=3)[N:9]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 86686713HCID 86686713, compound

Product 1

HCID 86686712{5-tert-Butyl-2-[2-(2-morpholin-4-yl-ethyl)-2H-indazol-6-yl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Intermediate 24b (86 mg, 0.23 mmol) in THF (10 mL) was added DIPEA (80 μL, 0.46 mmol), followed by the dropwise addition of a solution of 2,2,2-trichloroethylchloroformate (32 μL, 0.23 mmol) in THF (2 mL). The mixture was stirred at RT for 4 h, then partitioned between EtOAc/water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification by FCC, using 0-20% MeOH in EtOAc, gave the title compound (32 mg, 26%) as a yellow solid. LCMS (Method 4): Rt 2.64, 0.2 m/z 543, 545 [MH+].

Workup

  1. custompartitioned between EtOAc/water
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by FCC

Sources & evidence

ORD record
ord-751f7985ee46488d9808f15b2ddd1661
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

Loading…