Water → N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468725Notes

Reaction equation

HRID 468725 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]1[S:20][CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[N:23]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C.O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.ClCCl>[CH3:18][C:19]1[S:20][CH:21]=[C:22]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)[N:23]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 457863152-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazoleHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57410128N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamideYield 21.1%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (101 mg, 0.347 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (0.10 g, 0.44 mmol), potassium carbonate (147.9 mg, 1.070 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (24.3 mg, 0.0343 mmol) was added acetonitrile (3 mL, 60 mmol) and water (0.3 mL, 20 mmol). The reaction mixture was then stirred in a sealed vial at 90° C. for 8 hours, and then cooled to room temperature. The reaction mixture was poured into dichloromethane, washed once with saturated aqueous NaHCO3, dried over MgSO4, filtered, and evaporated in vacuo. The resulting residue was purified via reverse phase HPLC and lyophilized to yield 22.7 mg (21%) of N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.328, M+H=310.0, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.20 (s, 1H), 8.60 (s, 1H), 8.45 (s, 1H), 8.24 (dd, J=8.7, 1.5 Hz, 1H), 8.08 (s, 1H), 7.90 (d, J=8.7 Hz, 1H), 2.76 (s, 3H), 2.08 (ddd, J=12.2, 7.8, 4.7 Hz, 1H), 0.85 (dd, J=9.3, 6.3 Hz, 4H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed once with saturated aqueous NaHCO3
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe resulting residue was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-4899fc1f4c11410c94d8c9e33c6e9e9d
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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