Sodium Bicarbonate → 1-(2-(5-Chloro-4-(7-(pyridin-4-yl)benzo[b]thiophen-2-yl)pyrimidin-2-ylamino)ethyl)imidazolidin-2-one

HRID 422110Notes

Reaction equation

HRID 422110 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([NH:18][CH2:19][CH2:20][N:21]4[CH2:25][CH2:24][NH:23][C:22]4=[O:26])[N:12]=3)=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.[C:36](=[O:39])([OH:38])[O-:37].[Na+]>O.CS(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:36](=[O:37])([OH:39])[O-:38].[NH4+:12].[Cl:17][C:16]1[C:11]([C:9]2[S:8][C:7]3[C:2]([C:30]4[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=4)=[CH:3][CH:4]=[CH:5][C:6]=3[CH:10]=2)=[N:12][C:13]([NH:18][CH2:19][CH2:20][N:21]2[CH2:25][CH2:24][NH:23][C:22]2=[O:26])=[N:14][CH:15]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 666739751-{2-[4-(7-Bromo-benzo[b]thiophen-2-yl)-5-chloro-pyrimidin-2-ylamino]-ethyl}-imidazolidin-2-one

Product 2

HCID 14013Ammonium BicarbonateHCID 249380061-(2-(5-Chloro-4-(7-(pyridin-4-yl)benzo[b]thiophen-2-yl)pyrimidin-2-ylamino)ethyl)imidazolidin-2-oneYield 50.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Combine 1-{2-[4-(7-bromo-benzo[b]thiophen-2-yl)-5-chloro-pyrimidin-2-ylamino]-ethyl}-imidazolidin-2-one (81.6 mg, 0.18 mmol), pyridine-4-boronic acid (36.8 mg, 0.3 mmol), and sodium bicarbonate (18.1 mg, 0.2 mmol) in a mixture of water (1 mL) and DMSO (1 mL). Add tetrakis(triphenylphosphine)palladium(0) (10.4 mg, 0.009 mmol). Irradiate the mixture at 150° C. for 15 min with magnetic stirring. Pour the crude reaction mixture onto a strong cation exchange (SCX) (10 g) column. Elute the desired product with 2 N ammonia in methanol (40 mL) and concentrate under reduced pressure. Purify by reverse phase chromatography (30 to 90% gradient at 80 mL/min for 11 min on a 30×100 mm, 5 mm, C18 MS Xterra® column, Solvent A: water with 0.01 M ammonium bicarbonate, Solvent B: acetonitrile) to afford the title compound (20.4 mg, 25.1%). MS (ES) m/z 451 [M+1]+.

Workup

  1. customIrradiate the mixture at 150° C. for 15 min with magnetic stirring
  2. additionPour the crude
  3. customreaction mixture onto a strong cation exchange (SCX) (10 g) column
  4. washElute the desired product with 2 N ammonia in methanol (40 mL)
  5. concentrationconcentrate under reduced pressure
  6. customPurify by reverse phase chromatography (30 to 90% gradient at 80 mL/min for 11 min on a 30×100 mm, 5 mm

Sources & evidence

ORD record
ord-e9dcf52752104a868e11c74785ce8377
Source dataset
uspto-grants-2012_01
Patent number
US08101628B2

Reaction notes

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