(3S)-3-hydroxypyrrolidin-2-one → HCID 136232718, compound

HRID 1752264Notes

Reaction equation

HRID 1752264 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.O[C@H]1CCNC1=O.Cl[CH2:31][C:32]1[NH:33][C:34](=[O:42])[C:35]2[CH2:41][O:40][CH2:39][CH2:38][C:36]=2[N:37]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][N:17]([CH2:31][C:32]4[NH:33][C:34](=[O:42])[C:35]5[CH2:41][O:40][CH2:39][CH2:38][C:36]=5[N:37]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 11029774(3S)-3-hydroxypyrrolidin-2-oneHCID 71212217HCID 71212217, compound2×HCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 136232718HCID 136232718, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (0.165 mmol, 50 mg), which was prepared in a similar manner as (R)-3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one from (S)-3-hydroxypyrrolidin-2-one and 2-chloromethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.165 mmol, 33.2 mg) in THF (5 mL) was added 1 M solution of potassium hexamethyldisilylamide in THF (0.331 mmol, 0.331 mL) at −78° C. for 2 hours. The reaction was allowed to warm to 0° C. for 16 hours and evaporated under vacuum. The remaining residue was purified by flash column chromatography (silica) eluting over a gradient of 0-50% MeOH/ethyl acetate provided the title compound as an off-white solid (20 mg, 25.9% yield). HRMS calculated for C25H30N4O5 466.5417. found (ESI, [M+H]′) 467.2296. 1H NMR (400 MHz, MeOD) 8 ppm 1.69-1.91 (m, 4H) 2.10-2.33 (m, 2H) 2.49-2.59 (m, 1H) 2.59-2.67 (m, 2H) 2.76-2.89 (m, 1H) 2.91-3.01 (m, 1H) 3.11-3.22 (m, 1H) 3.32-3.44 (m, 2H) 3.46-3.58 (m, 2H) 3.59-3.71 (t, J=8.78 Hz, 1H) 3.88-3.96 (m, 2H) 4.04-4.14 (d, J=15.56 Hz, 2H) 4.36-4.42 (m, 2H) 4.44-4.51 (m, 2H) 6.97 (d, J=9.03 Hz, 2H) 7.92 (d, J=9.03 Hz, 2H), analytical RP-HPLC retention time=4.02 min.

Workup

  1. customevaporated under vacuum
  2. customThe remaining residue was purified by flash column chromatography (silica)
  3. washeluting over a gradient of 0-50% MeOH/ethyl acetate

Sources & evidence

ORD record
ord-177ae63c4b934025a58e0e4cb48bf4d5
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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