Sodium hydride → 2-((3-(5-methoxy-1-oxo-1,3-dihydrospiro[indene-2,4'-piperidine]-1'-yl)-2-oxopyrrolidin-1-yl)methyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-one

HRID 1752270Notes

Reaction equation

HRID 1752270 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:20](=[CH:21][CH:22]=1)[C:19](=[O:23])[C:7]1([CH2:12][CH2:11][N:10]([CH:13]3[CH2:17][CH2:16][NH:15][C:14]3=[O:18])[CH2:9][CH2:8]1)[CH2:6]2.Cl[CH2:25][C:26]1[NH:27][C:28](=[O:36])[C:29]2[CH2:35][O:34][CH2:33][CH2:32][C:30]=2[N:31]=1.[H-].[Na+]>C1COCC1.CN(C=O)C.CCOCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:20](=[CH:21][CH:22]=1)[C:19](=[O:23])[C:7]1([CH2:8][CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][N:15]([CH2:25][C:26]4[NH:27][C:28](=[O:36])[C:29]5[CH2:35][O:34][CH2:33][CH2:32][C:30]=5[N:31]=4)[C:14]3=[O:18])[CH2:11][CH2:12]1)[CH2:6]2

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 71212278HCID 71212278, compoundHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 1362327252-((3-(5-methoxy-1-oxo-1,3-dihydrospiro[indene-2,4'-piperidine]-1'-yl)-2-oxopyrrolidin-1-yl)methyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-oneYield 41.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 5-methoxy-1′-(2-oxopyrrolidin-3-yl)spiro[indene-2,4′-piperidin]-1(3H)-one (3.34 mmol, 1.05 g) and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (3.67 mmol, 0.737 g) in THF (40 mL) and DMF (5 mL) was added sodium hydride (60%, 11.69 mmol, 0.468 g) and the suspension was heated at 70° C. for 45 min. The reaction was allowed to cool to ambient temperature, diluted with 100 mL of ether, an off-white solid was collected by filtration and was dried in vacuo. Recrystallization from isopropyl alcohol/methyl alcohol provided the title compound as an off-white solid (661 mg, 41.4% yield). Calculated MS=478.6, MS (ESI) m/e 479.0 (M+H+); 1H NMR (400 MHz, MeOD) 8 ppm 1.33-1.46 (m, 2H) 1.92-2.07 (m, 2H) 2.07-2.27 (m, 2H) 2.49-2.65 (m, 3H) 2.89 (dd, J=8.53, 2.51 Hz, 2H) 3.02-3.15 (m, 3H) 3.35-3.50 (m, 2H) 3.70 (t, J=8.78 Hz, 1H) 3.85-3.98 (m, 6H) 4.16 (d, J=15.06 Hz, 1H) 4.44-4.53 (m, 3H) 6.96 (dd, J=8.53, 2.51 Hz, 1H) 7.05 (s, 1H) 7.62 (d, J=9.03 Hz, 1H). HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.391 min.

Workup

  1. temperatureto cool to ambient temperature
  2. filtrationan off-white solid was collected by filtration
  3. customwas dried in vacuo
  4. customRecrystallization from isopropyl alcohol/methyl alcohol

Sources & evidence

ORD record
ord-fe533369f2174c3f84fe334a63ffa134
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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