Sodium Carbonate → N-(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

HRID 887411Notes

Reaction equation

HRID 887411 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[S:17][C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[N:20]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[CH3:25][C:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][N:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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].C(Cl)Cl>[CH3:25][C:26]1[CH:31]=[C:30]([C:2]2[C:3]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]4[S:17][C:18]5[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=5[N:20]=4)=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH:29]=[CH:28][N:27]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 59351351N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

Product 1

HCID 59351437N-(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of N-(4-(3-chloropyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine (180 mg, 0.507 mmol), 2-methylpyridin-4-ylboronic acid (278 mg, 2.03 mmol), PdCl2(dppf)-CH2Cl2 adduct (41.4 mg, 0.051 mmol), and sodium carbonate (323 mg, 3.04 mmol) in 1,4-dioxane (3 mL) and water (2 mL) was sparged with argon for 5 min, then heated to 100° C. for 2 h. The reaction mixture was partitioned between EtOAc and 1M NaOH. The aqueous layer was extracted with EtOAc (2×) and the combined organics was dried over Na2SO4 and concentrated. The crude material was absorbed on Silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 70% EtOAc in hexane, to provide N-(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)benzo[d]thiazol-2-amine as white solid. MS (ESI, pos. ion) m/z: 412.0 (M+1). IC50 (uM) +++++.

Workup

  1. customwas sparged with argon for 5 min
  2. customThe reaction mixture was partitioned between EtOAc and 1M NaOH
  3. extractionThe aqueous layer was extracted with EtOAc (2×)
  4. dry with materialthe combined organics was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude material was absorbed on Silica gel
  7. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 0% to 70% EtOAc in hexane

Sources & evidence

ORD record
ord-fe98d9d665204bfb99cf373916ad621c
Source dataset
uspto-grants-2012_08
Patent number
US08247418B2

Reaction notes

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