Ammonia → 8'-{[(2S)-2-(Methoxymethyl)pyrrolidinyl]sulfonyl}-3',4'-dihydrospiro(1,3-dioxane-2,10' (2'H)-pyrimido(1,2-a)indole)

HRID 853844Notes

Reaction equation

HRID 853844 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)[N:17]([CH2:21][CH2:22][C:23]#[N:24])[C:16](=O)[C:15]12[O:30][CH2:29][CH2:28][CH2:27][O:26]1)(=[O:11])=[O:10].N.C1COCC1.[H][H]>[Ni].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[CH2:21][CH2:22][CH2:23][N:24]=[C:16]3[C:15]3([O:26][CH2:27][CH2:28][CH2:29][O:30]3)[C:14]=2[CH:13]=1)(=[O:11])=[O:10]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 8028TetrahydrofuranHCID 589325773-[5'-{[(2S)-2-(Methoxymethyl)pyrrolidin-1-yl]sulfonyl}-2'-oxospiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]propanenitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 115462928'-{[(2S)-2-(Methoxymethyl)pyrrolidinyl]sulfonyl}-3',4'-dihydrospiro(1,3-dioxane-2,10' (2'H)-pyrimido(1,2-a)indole)Yield 14.5%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 3-[5′-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′ (2′H)-yl]propanenitrile (4.48 g, 10.3 mmol), and wet Raney nickel (4.1 g) in 2M EtOH.NH3 (100 mL) and THF (100 mL) was hydrogenated in a Parr Hydrogenation Bottle (2L) at 45 lb/in2 hydrogen for 24 hours. The Raney nickel was removed by filtration through Sulka Floc. The filtrate was poured into a steel pressure vessel and heated to 135° C. for 51 hours. The reaction was cooled and the solvents were removed. The residue was taken up in CH2Cl2 and combined with silica gel. The solvent was removed and the adsorbate was flash chromatographed (Biotage KP silica gel, and step gradient of CH2Cl2/CH3OH/NH4OH (98.5/1.0/0.5-98/01.5/0.5)) to give the title compound as a white solid (0.63 g, 14.5% yield). Anal: Calc'd. for C20H27N3O5S: C, 56.99; H, 6.46; N, 9.97; Found: C, 56.80, H, 6.45, N, 9.87; NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 422 [M+H]. Opt. Rotation: 94.1(calculated) at 25° C. in CH3OH (1% concentration), wavelength 589; m.p. 129-130°.

Workup

  1. customfor 24 hours
  2. customThe Raney nickel was removed by filtration through Sulka Floc
  3. additionThe filtrate was poured into a steel pressure vessel
  4. temperatureThe reaction was cooled
  5. customthe solvents were removed
  6. customThe solvent was removed
  7. customchromatographed (Biotage KP silica gel, and step gradient of CH2Cl2/CH3OH/NH4OH (98.5/1.0/0.5-98/01.5/0.5))

Sources & evidence

ORD record
ord-834b1f2475e24eee945bdbc4b0a20ac0
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

Loading…