Water → (R)-tert-Butyl 3-(4-(2-(cyclopropanecarboxamido)pyrazolo[1,5-a]pyridin-4-yl)phenoxy)pyrrolidine-1-carboxylate

HRID 873337Notes

Reaction equation

HRID 873337 reaction equation
Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[CH:43]=[CH:42][C:28]([O:29][C@@H:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]3)=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1>[CH:14]1([C:12]([NH:11][C:9]2[CH:10]=[C:3]3[C:2]([C:25]4[CH:43]=[CH:42][C:28]([O:29][C@@H:30]5[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[CH2:31]5)=[CH:27][CH:26]=4)=[CH:7][CH:6]=[CH:5][N:4]3[N:8]=2)=[O:13])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 70979567N-(4-bromopyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamideHCID 86710535(R)-tert-butyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrrolidine-1-carboxylate

Product 1

HCID 86710536(R)-tert-Butyl 3-(4-(2-(cyclopropanecarboxamido)pyrazolo[1,5-a]pyridin-4-yl)phenoxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

N-(4-Bromopyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide (265 mg, 0.95 mmol), (R)-tert-butyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrrolidine-1-carboxylate (442 mg, 1.14 mmol), PdCl2dppf (39 mg, 0.047 mmol) and Na2CO3 (501 mg, 4.73 mmol) were stirred in 1,4-dioxane (15 ml) and water (3 ml) and heated at 100° C. for 2 h. The reaction mixture was cooled to room temperature and filtered through celite. The residue was partitioned between EtOAc and water and the aqueous phase was extracted with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated in vacuo to give (R)-tert-Butyl 3-(4-(2-(cyclopropanecarboxamido)pyrazolo[1,5-a]pyridin-4-yl)phenoxy)pyrrolidine-1-carboxylate as a brown oil which was used in the next step without further purification.

Workup

  1. filtrationfiltered through celite
  2. customThe residue was partitioned between EtOAc and water
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-df30dcaca0aa44a094237461751cc708
Source dataset
uspto-grants-2015_03
Patent number
US08975406B2

Reaction notes

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