Sodium Iodide → 1-(3-(5-Chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propyl)-5-(thiophen-2-yl)pyrimidine-2,4(1h,3h)-dione hydrochloride

HRID 1661081Notes

Reaction equation

HRID 1661081 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:10]=[C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[C:8](=[O:16])[NH:7][C:6]1=[O:17].Cl.[Cl:19][C:20]1[CH:21]=[C:22]2[C:30](=[CH:31][CH:32]=1)[C:25]1([CH2:29][CH2:28][NH:27][CH2:26]1)[CH2:24][CH2:23]2.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>O.CN1C(=O)CCC1>[ClH:1].[Cl:19][C:20]1[CH:21]=[C:22]2[C:30](=[CH:31][CH:32]=1)[C:25]1([CH2:29][CH2:28][N:27]([CH2:2][CH2:3][CH2:4][N:5]3[CH:10]=[C:9]([C:11]4[S:12][CH:13]=[CH:14][CH:15]=4)[C:8](=[O:16])[NH:7][C:6]3=[O:17])[CH2:26]1)[CH2:24][CH2:23]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 593375931-(3-chloropropyl)-5-(2-thienyl)-2,4(1H,3H)-pyrimidinedioneHCID 674279925-Chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine] hydrochloride

Product 1

HCID 674297191-(3-(5-Chloro-2,3-dihydrospiro[indene-1,3'-pyrrolidine]-1'-yl)propyl)-5-(thiophen-2-yl)pyrimidine-2,4(1h,3h)-dione hydrochlorideYield 81.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(3-chloropropyl)-5-(thiophen-2-yl)pyrimidine-2,4(1H,3H)-dione (Prep24, 50 mg, 0.18 mmol), 5-chloro-2,3-dihydrospiro[indene-1,3′-pyrrolidine]hydrochloride salt (Prep10, 66 mg, 0.27 mmol), potassium carbonate (112 mg, 0.81 mmol), sodium iodide (112 mg, 0.75 mmol) and NMP (1 ml) was stirred at 70° C. overnight. Then it was cooled down to room temperature and diluted with water and extracted with ethyl acetate. The EA phase was evaporated and the crude purified by preparative TLC (TLC analysis performed by eluting with EA/MeOH 10:1) to give the free base of the title compound (70 mg). The compound was purified by preparative HPLC and treated with a 1N solution of HCl-ether to give the title compound (9 mg, y=10%).

Workup

  1. temperatureThen it was cooled down to room temperature
  2. extractionextracted with ethyl acetate
  3. customThe EA phase was evaporated
  4. customthe crude purified by preparative TLC (TLC analysis performed by eluting with EA/MeOH 10:1)

Sources & evidence

ORD record
ord-3b11f6e5cd354543a48dc77cdd1079c6
Source dataset
uspto-grants-2011_10
Patent number
US08030322B2

Reaction notes

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