Sodium Hydroxide → 2,4-Difluoro-N-[5-(4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl]benzenesulfonamide

HRID 520639Notes

Reaction equation

HRID 520639 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:14]([O:52][CH3:53])=[N:15][CH:16]=[C:17]([C:19]2[CH:27]=[C:26]3[C:22]([CH:23]=[N:24][N:25]3S(C3C=CC=CC=3)(=O)=O)=[C:21]([C:37]3[O:38][C:39]([CH2:42][N:43]4[CH2:48][CH2:47][N:46]5[CH2:49][CH2:50][CH2:51][C@H:45]5[CH2:44]4)=[N:40][N:41]=3)[CH:20]=2)[CH:18]=1)(=[O:11])=[O:10].[OH-].[Na+]>O1CCOCC1.CS(C)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:14]([O:52][CH3:53])=[N:15][CH:16]=[C:17]([C:19]2[CH:27]=[C:26]3[C:22]([CH:23]=[N:24][NH:25]3)=[C:21]([C:37]3[O:38][C:39]([CH2:42][N:43]4[CH2:48][CH2:47][N:46]5[CH2:49][CH2:50][CH2:51][C@H:45]5[CH2:44]4)=[N:40][N:41]=3)[CH:20]=2)[CH:18]=1)(=[O:11])=[O:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 666915602,4-Difluoro-N-[5-[4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamide

Product 1

HCID 666915722,4-Difluoro-N-[5-(4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl]benzenesulfonamideYield 3.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Procedure

2,4-Difluoro-N-[5-[4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamide (84 mg, 0.110 mmol) was dissolved in 1,4-dioxane (1 ml) and sodium hydroxide (1 ml, 0.110 mmol) was added. The mixture was stirred at room temperature for 1 h. The mixture was dried down under a stream of nitrogen and the residue partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml). The organic layer was separated, dried by passing through a hydrophobic frit and the solvent removed in vacuo to give a brown gum. This was dissolved in DMSO (1 ml) and purified by high pH MDAP (Method E, extended run). The product-containing fraction was dried under a stream of nitrogen to give the title compound as a cream solid (2.4 mg).

Workup

  1. customThe mixture was dried down under a stream of nitrogen
  2. customthe residue partitioned between ethyl acetate (5 ml) and saturated ammonium chloride (2 ml)
  3. customThe organic layer was separated
  4. customdried
  5. customthe solvent removed in vacuo
  6. customto give a brown gum
  7. custompurified by high pH MDAP (Method E, extended run)
  8. customThe product-containing fraction was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-a05d2c18ef6a44e9a98c0f74f1a58ca2
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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