Triethylamine → (R)-N-(4-(4-((1-(methylsulfonyl)pyrrolidin-3-yl)oxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

HRID 873339Notes

Reaction equation

HRID 873339 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[C:14]4[N:15]([N:19]=[C:20]([NH:22][C:23]([CH:25]5[CH2:27][CH2:26]5)=[O:24])[CH:21]=4)[CH:16]=[CH:17][CH:18]=3)=[CH:9][CH:8]=2)[CH2:2]1.C(N(CC)CC)C.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C(Cl)Cl>[CH3:35][S:36]([N:1]1[CH2:5][CH2:4][C@@H:3]([O:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]3[C:14]4[N:15]([N:19]=[C:20]([NH:22][C:23]([CH:25]5[CH2:26][CH2:27]5)=[O:24])[CH:21]=4)[CH:16]=[CH:17][CH:18]=3)=[CH:11][CH:12]=2)[CH2:2]1)(=[O:38])=[O:37]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 70979103(R)-N-(4-(4-(pyrrolidin-3-yloxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 70979866(R)-N-(4-(4-((1-(methylsulfonyl)pyrrolidin-3-yl)oxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(R)—N-(4-(4-(pyrrolidin-3-yloxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide (340 mg, 0.94 mmol) and triethylamine (0.16 ml, 1.13 mmol) were suspended in DCM (10 ml) and stirred at 0° C. under N2. Methane sulfonylchloride (77 μL, 0.99 mmol) was added slowly and the resulting solution was allowed to warm to room temperature over 4 h. The reaction mixture was washed with sat. NaHCO3 solution (aq.) and the aqueous phase extracted with DCM. The combined organics were dried (MgSO4), filtered, concentrated in vacuo and purified by preparative HPLC to give (R)—N-(4-(4-((1-(methylsulfonyl)pyrrolidin-3-yl)oxy)phenyl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide. (126 mg, 30% yield).

Workup

  1. temperatureto warm to room temperature over 4 h
  2. washThe reaction mixture was washed with sat. NaHCO3 solution (aq.)
  3. extractionthe aqueous phase extracted with DCM
  4. dry with materialThe combined organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-497bfc48b1254cfe8b72962b5ff305aa
Source dataset
uspto-grants-2015_03
Patent number
US08975406B2

Reaction notes

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