Diisopropylethylamine → N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-(3-cyclopropyl-3-fluoroazetidin-1y1)pyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamide

HRID 390425Notes

Reaction equation

HRID 390425 reaction equation
[S:1]1[C:5]([NH:6][C:7]2[CH:12]=[C:11](Cl)[N:10]=[C:9]([S:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:28])[CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:17][CH:16]=3)[N:8]=2)=[N:4][CH:3]=[N:2]1.Cl.[CH:30]1([C:33]2([F:37])[CH2:36][NH:35][CH2:34]2)[CH2:32][CH2:31]1.CCN(C(C)C)C(C)C>O1CCOCC1>[S:1]1[C:5]([NH:6][C:7]2[CH:12]=[C:11]([N:35]3[CH2:36][C:33]([CH:30]4[CH2:32][CH2:31]4)([F:37])[CH2:34]3)[N:10]=[C:9]([S:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:28])[CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:17][CH:16]=3)[N:8]=2)=[N:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 59450317N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamideHCID 665896423-Cyclopropyl-3-fluoroazetidine hydrochloride

Product 1

HCID 25052722N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-(3-cyclopropyl-3-fluoroazetidin-1y1)pyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamideYield 20.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a microwave tube was added N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)-3,3,3-trifluoropropanamide (100 mg, 0.25 mmol), 3-cyclopropyl-3-fluoroazetidine hydrochloride (100 mg, 0.7 mmol), DIPEA (0.1 ml) and dioxane. The mixture was microwaved at 130 C for 20 mins, partitioned between ethylacetate and bicarbonate and organic layer concentrated to an oil. The product was purified by HPLC to afford the product as a white solid (27 mg, 20%) 1H NMR d6 DMSO 0.42-0.48 (2H, m), 0.6-0.63 (2H, m), 1.38-1.43 (1H, m), 3.55-3.65 (2H, m), 3.8-4.0 (4H, m), 5.65 (1H,s), 7.65 (2H, d), 7.75 (2H, d), 8.2 (1H,s), 10.7 (1H,s), 12.1 (1H,s); MS ESI+ve 526 (M+H)+.

Workup

  1. customThe mixture was microwaved at 130 C for 20 mins
  2. custompartitioned between ethylacetate and bicarbonate and organic layer
  3. concentrationconcentrated to an oil
  4. customThe product was purified by HPLC

Sources & evidence

ORD record
ord-cfd48b656e9b408280c7a39c759f0c2f
Source dataset
uspto-grants-2013_02
Patent number
US08383633B2

Reaction notes

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