Water → 8-{[(2S)-2-(Methoxymethyl)pyrrolidin-1-yl]sulfonyl}-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one

HRID 853843Notes

Reaction equation

HRID 853843 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=O)[C:15]12OCCC[O:22]1)(=[O:11])=[O:10].[OH-].[CH2:28]([N+:35](C)(C)C)[C:29]1C=CC=C[CH:30]=1.O.C(Cl)Cl.CO>CCO>[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:20]=[CH:19][C:18]2[N:17]3[CH2:30][CH2:29][CH2:28][N:35]=[C:16]3[C:15](=[O:22])[C:14]=2[CH:13]=1)(=[O:11])=[O:10]

Participants

6

Reactant 4

HCID 962WaterHCID 66854Benzyltrimethylammonium hydroxideHCID 21226129Dichloromethane methanolHCID 589325505'-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

Product 1

HCID 115667308-{[(2S)-2-(Methoxymethyl)pyrrolidin-1-yl]sulfonyl}-3,4-dihydropyrimido[1,2-a]indol-10(2H)-oneYield 290%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
59 °C

Procedure

A suspension of 5′-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (6.8 g, 17.8 mmol) and benzyltrimethyl-ammonium hydroxide (40% by weight aqueous solution, 1.94 mL, 4.27 mmol, 0.25 eq) in absolute EtOH (80 mL) was heated to 59° C. and acryonitrile (2.93 mL, 44.5 mmol, 2.5 eq) was added drop-wise. After heating 5 hrs at 72° C. the reaction was cooled to room temperature, poured into H2O (160 mL) and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was flash chromatographed (Biotage KP silica gel, 99/1 then 98/2 CH2Cl2/CH3OH) to give the title compound as a white solid (4.5 g, 58% yield). Anal: Calc'd for C20H25N3O6S: C, 55.16; H, 5.79; N, 9.65; Found: C, 55.06, H, 5.94, N, 9.52; NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 436[M+H] m.p.: 138-141° C.

Workup

  1. additionwas added drop-wise
  2. temperatureAfter heating 5 hrs at 72° C. the reaction
  3. temperaturewas cooled to room temperature
  4. extractionextracted with EtOAc (3×150 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed (Biotage KP silica gel, 99/1

Sources & evidence

ORD record
ord-789786f192514ffb9c41fa35834df950
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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