Dichloromethane → 1-{5-[2-(3-Ethyl-ureido)-7-vinyl-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester

HRID 712259Notes

Reaction equation

HRID 712259 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH3:34])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20](Br)[C:21]4[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:35][C:36]1(C)C(C)(C)OB(C=C)O1.C(Cl)Cl.[F-].[K+]>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].O.O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1([CH3:34])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:35]=[CH2:36])[C:21]4[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 522689Potassium FluorideHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 866639721-{5-[2-(3-Ethyl-ureido)-7-vinyl-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl esterYield 124%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

1-{5-[7-Bromo-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester (50 mg), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (28 mg), PdCl2(dppf).DCM (4 mg), potassium fluoride (16 mg), 1,4-dioxane (1.5 mL) and water (0.5 mL) were combined in a 0.5-2 mL microwave vial, degassed and heated in a pre-heated oil bath at 90° C. overnight. The mixture was cooled to rt, diluted with water and extracted into EtOAc (4×10 mL). The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by Biotage Si chromatography, 12 g Grace cartridge, 4-5% MeOH in DCM. The relevant fractions were combined to give a solid (56 mg) which was purified again by Biotage Si chromatography, 12 g Grace cartridge, 2% MeOH in DCM isocratic. The relevant fractions were combined to give the desired product as a light orange solid (27 mg, 60%). m/z: 495 [M+H]+.

Workup

  1. customdegassed
  2. temperatureThe mixture was cooled to rt
  3. additiondiluted with water
  4. extractionextracted into EtOAc (4×10 mL)
  5. washThe organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by Biotage Si chromatography, 12 g Grace cartridge, 4-5% MeOH in DCM

Sources & evidence

ORD record
ord-299b9766ddda45d5bae44bc0d3f7e5cf
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

Loading…