1-Hydroxybenzotriazole → HCID 66743834, compound

HRID 2364007Notes

Reaction equation

HRID 2364007 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[S:15][C:14]3[C:13](=[O:16])[NH:12][C:11]4([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)[NH:10][C:9]=3[CH:8]=2)=[CH:3][CH:2]=1.[OH:22]N1C2C=CC=CC=2N=N1.Cl.[CH2:33]([N:35]=C=NCCCN(C)C)[CH3:34]>C(OC(NCC(O)=O)=O)(C)(C)C.CN(C=O)C>[NH2:35][CH2:33][C:34]([N:19]1[CH2:20][CH2:21][C:11]2([NH:10][C:9]3[CH:8]=[C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[S:15][C:14]=3[C:13](=[O:16])[NH:12]2)[CH2:17][CH2:18]1)=[O:22]

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66742948HCID 66742948, compound

Product 1

HCID 66743834HCID 66743834, compoundYield 2.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 78288N-(tert-butoxycarbonyl)glycineSolvent

Procedure

A mixture of 6′-(pyridin-4-yl)-1′H-spiro[piperidine-4,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one in DMF (0.16 M, 0.50 mL, 0.080 mmol), N-(tert-butoxycarbonyl)glycine in DMF (0.192 M, 0.50 mL, 0.096 mmol) and a solution of 1-hydroxybenzotriazole and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in DMF (0.192 M, 0.50 mL, 0.096 mmol for each) was stirred for 16 h at room temperature. The reaction mixture was extracted with EtOAc (3.5 mL) and 2% aqueous sodium hydrogen carbonate (1 mL). After evaporating the organic solvent, 1 M methanesulfonic acid in MeCN (0.5 mL) was added to the residue. The mixture was stirred for 16 h at room temperature. After neutralizing the reaction mixture with 1 M N-ethyl-N-(1-methylethyl)propan-2-amine (0.5 mL), the crude product was chromatographed on preparative HPLC (YMC CombiPrep. Hydrosphere C18, 10 mM NH4HCO3 in water/MeCN) to afford the title compound (0.8 mg, 2.8%):

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3.5 mL) and 2% aqueous sodium hydrogen carbonate (1 mL)
  2. customAfter evaporating the organic solvent, 1 M methanesulfonic acid in MeCN (0.5 mL)
  3. additionwas added to the residue
  4. customthe crude product was chromatographed on preparative HPLC (YMC CombiPrep. Hydrosphere C18, 10 mM NH4HCO3 in water/MeCN)

Sources & evidence

ORD record
ord-536f20c17bdf4b1da2453322a7dad489
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

Loading…