Dichloromethane → 1-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanesulfonamide

HRID 410603ノート

反応式

HRID 410603 の反応式
Br[C:2]1[S:6][C:5]([CH2:7][S:8]([NH2:11])(=[O:10])=[O:9])=[N:4][CH:3]=1.[CH3:12][C:13]1[CH:14]=[C:15]([NH:28][C:29]2[N:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=2)[CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH3:12][C:13]1[CH:18]=[C:17]([C:2]2[S:6][C:5]([CH2:7][S:8]([NH2:11])(=[O:10])=[O:9])=[N:4][CH:3]=2)[CH:16]=[C:15]([NH:28][C:29]2[N:34]=[C:33]([C:35]([F:38])([F:36])[F:37])[CH:32]=[CH:31][N:30]=2)[CH:14]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine2 回HCID 67257311(5-Bromo-1,3-thiazol-2-yl)methanesulfonamide

生成物 1

HCID 584561961-[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanesulfonamide収率 71%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

The product of Step 4 (102 mg, 0.396 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 3, 150 mg, 0.396 mmol), and PdCl2(dppf).CH2Cl2 (29 mg, 0.040 mmol) were combined in a flask, sealed, and purged with nitrogen (2×). Dioxane (2.4 mL) and aqueous Na2CO3 (2 M, 0.593 mL, 1.187 mmol) were added, and the reaction was purged again with nitrogen (2×). The mixture was stirred in an oil bath at 100° C. overnight. The dark brown reaction was diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (dry load, 25-100% ethyl acetate in hexanes) provided an orange solid that was triturated with CH2Cl2 and filtered to afford 1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanesulfonamide (120 mg, 71%) as a colorless solid. MS ESI: [M+H]+ m/z 430.0. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.83 (d, J=4.9, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.50 (s, 1H), 7.28 (d, J=4.9, 1H), 7.20 (s, 1H), 7.17 (s, 2H), 4.73 (s, 2H), 2.32 (s, 3H). rhSYK activity=+++

後処理

  1. customsealed
  2. custompurged with nitrogen (2×)
  3. customthe reaction was purged again with nitrogen (2×)
  4. customThe dark brown reaction
  5. extractionextracted with ethyl acetate (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. dry with materialFlash chromatography (dry load, 25-100% ethyl acetate in hexanes)
  11. customprovided an orange solid
  12. customthat was triturated with CH2Cl2
  13. filtrationfiltered

出典と根拠

ORDレコード
ord-772269a37afc4121a89470525d92df4c
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

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