hydroxylamine-O-sulfonic acid → 3-Methyl-2-(5-(5-sulfamoyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide

HRID 510204Notes

Reaction equation

HRID 510204 reaction equation
[CH3:1][CH:2]([CH3:45])[CH:3]([NH:12][C:13]1[CH:14]=[C:15]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([S:28](CCC(OC)=O)(=[O:30])=[O:29])[CH:26]=3)[N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:20]=2)[CH:16]=[N:17][CH:18]=1)[C:4](=[O:11])[NH:5][CH2:6][C:7]([F:10])([F:9])[F:8].C1CCN2C(=[N:50]CCC2)CC1.NOS(O)(=O)=O.C([O-])(=O)C.[Na+]>CS(C)=O.O>[CH3:1][CH:2]([CH3:45])[CH:3]([NH:12][C:13]1[CH:18]=[N:17][CH:16]=[C:15]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([S:28](=[O:30])(=[O:29])[NH2:50])[CH:26]=3)[N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:20]=2)[CH:14]=1)[C:4]([NH:5][CH2:6][C:7]([F:10])([F:9])[F:8])=[O:11]

Participants

7

Reactant 4

HCID 76284hydroxylamine-O-sulfonic acid2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 517045Sodium Acetate2×HCID 123152589HCID 123152589, compound

Product 1

HCID 894953863-Methyl-2-(5-(5-sulfamoyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamideYield 89.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

To a mixture of methyl 3-(3-(5-(3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylamino)pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-5-ylsulfonyl)propanoate 4-1d (300 mg, 0.447 mmol) in DMSO (1.2 ml) was added DBU (0.135 ml, 0.893 mmol) and the reaction allowed to stir for 15 min. A solution of hydroxylamine-o-sulfonic acid (253 mg, 2.233 mmol) and sodium acetate (147 mg, 1.786 mmol) in water (0.8 mL) was added. The cloudy oily mixture was allowed to stir at RT for ½ hrs and then an additional charge of sodium acetate (147 mg, 1.786 mmol) and hydroxylamine-o-sulfonic acid (253 mg, 2.233 mmol) added and the mixture warmed to 40° C. for 2 hrs. The reaction was diluted with water (30 mL) and product extracted with ethyl acetate (50 ml), dried over sodium sulfate, filtered and concentrated to an oil. The oil was dissolved in DCM and chromatographed on silica (25 gm, using 2-10% methanol/DCM to give the desired product 4-1e as a white solid (240 mg). LRMS (ESI) m/z 601.2 [(M+H)+; calcd for C25H35F3N6O4SSi: 601.2].

Workup

  1. stirringto stir at RT for ½ hrs
  2. additionadded
  3. extractionextracted with ethyl acetate (50 ml)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. dissolutionThe oil was dissolved in DCM
  8. customchromatographed on silica (25 gm

Sources & evidence

ORD record
ord-52ca382cbf574f189ad4635c8e2a97b9
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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