Dichloromethane → N-(4-(4-(3-Cyclopropyl-3-fluoroazetidin-1-yl)-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide

HRID 390428Notes

Reaction equation

HRID 390428 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:5]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]3[CH2:27][CH2:26]3)=[O:24])=[CH:18][CH:17]=2)[N:3]=1.Cl.[CH:29]1([C:32]2([F:36])[CH2:35][NH:34][CH2:33]2)[CH2:31][CH2:30]1.CCN(C(C)C)C(C)C.ClCCl>O1CCOCC1>[CH:29]1([C:32]2([F:36])[CH2:35][N:34]([C:2]3[CH:7]=[C:6]([NH:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=4)[N:5]=[C:4]([S:15][C:16]4[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]5[CH2:27][CH2:26]5)=[O:24])=[CH:18][CH:17]=4)[N:3]=3)[CH2:33]2)[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 665896423-Cyclopropyl-3-fluoroazetidine hydrochlorideHCID 86644546N-(4-(4-Chloro-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropane carboxamide

Product 1

HCID 25117157N-(4-(4-(3-Cyclopropyl-3-fluoroazetidin-1-yl)-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Prepared according the procedure used for the synthesis of compound I-1, starting with N-(4-(4-Chloro-6-(pyridin-2-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropane carboxamide (110 mg, 28 mmol), 3-cyclopropyl-3-fluoroazetidine hydrochloride (60 mg, 0.39 mmol), and DiPEA (0.15 mL, 0.9 mmol) in 1,4-dioxane. After column chromatography, the product containing fraction (TLC: SiO2, dichloromethane/7.5% 2-propanol, Rf=0.65; HPLC: 70/90% purity, Rf=8.813 minutes) was purified further by preparative HPLC to yield 4 mg after evaporation and lyophilization with a purity of 96+% (HPLC method B, Rf=5.841 minutes).

Workup

  1. customPrepared
  2. customused for the synthesis of compound I-1
  3. customwas purified further by preparative HPLC
  4. customto yield 4 mg
  5. customafter evaporation and lyophilization with a purity of 96+% (HPLC method B, Rf=5.841 minutes)

Sources & evidence

ORD record
ord-0369b9850d1a4b639972a2bc6a4447c5
Source dataset
uspto-grants-2013_02
Patent number
US08383633B2

Reaction notes

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