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

HRID 1040083Notes

Reaction equation

HRID 1040083 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([S:10]([NH2:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=1.[N+:14]([C:17]1[CH:18]=[C:19]([NH:32][C:33]2[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=2)[CH:20]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=1)([O-:16])=[O:15].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>[N+:14]([C:17]1[CH:22]=[C:21]([C:2]2[S:6][C:5]([C:7]([S:10]([NH2:13])(=[O:12])=[O:11])([CH3:9])[CH3:8])=[N:4][CH:3]=2)[CH:20]=[C:19]([NH:32][C:33]2[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=2)[CH:18]=1)([O-:16])=[O:15]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 58456316N-[3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×HCID 672570342-(5-Bromothiazol-2-yl)propane-2-sulfonamide

Product 1

HCID 584562412-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl)propane-2-sulfonamideYield 74%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The product of Step 5 (174 mg, 0.61 mmol), N-[3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 12, 250 mg, 0.61 mmol), and PdCl2(dppf).CH2Cl2 (44.6 mg, 0.061 mmol) were combined in a flask, sealed, and purged with nitrogen (2×). Dioxane (3.6 mL) and 2 M Na2CO3 (0.91 mL, 1.83 mmol) were added, and the reaction was purged again with nitrogen (2×). The mixture was stirred in an oil bath at 100° C. for 4 h. 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, 20-100% ethyl acetate in hexanes) afforded 220 mg (74%) of 2-[5-(3-nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propane-2-sulfonamide as a yellow solid. ESI: [M+H]+ m/z 489.0. 1H NMR (500 MHz, DMSO-d6) δ 10.80 (s, 1H), 8.94 (d, J=4.9, 1H), 8.72 (s, 1H), 8.48 (s, 1H), 8.33 (s, 1H), 8.14 (s, 1H), 7.43 (d, J=4.9, 1H), 7.10 (s, 2H), 1.81 (s, 6H). rhSYK activity=++

Workup

  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, 20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f9c2e88a87ea4699ad84172a5d3ccf04
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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