Water → 3-{[1,1-dioxido-2-(phenylmethyl)-3,4-dihydro-2H-5,1,2-benzoxathiazepin-7-yl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548677Notes

Reaction equation

HRID 548677 reaction equation
CC([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[S:10]([C:13]1[CH:18]=[CH:17][C:16](F)=[CH:15][C:14]=1F)(=[O:12])=[O:11])(C)C.[OH:30][C:31]1[CH:32]=[C:33]([CH:43]=[C:44]([O:46][C@@H:47]([CH3:60])[CH2:48][O:49][Si](C(C)C)(C(C)C)C(C)C)[CH:45]=1)[C:34]([NH:36][C:37]1[CH:41]=[CH:40][N:39]([CH3:42])[N:38]=1)=[O:35].C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[O:12]=[S:10]1(=[O:11])[C:13]2[CH:14]=[CH:15][C:16]([O:30][C:31]3[CH:32]=[C:33]([CH:43]=[C:44]([O:46][C@@H:47]([CH3:60])[CH2:48][OH:49])[CH:45]=3)[C:34]([NH:36][C:37]3[CH:41]=[CH:40][N:39]([CH3:42])[N:38]=3)=[O:35])=[CH:17][C:18]=2[O:6][CH2:7][CH2:8][N:9]1[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 536296193-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-[((1S)-1-methyl-2-{[tris(1-methylethyl)silyl]oxy}ethyl)oxy]benzamideHCID 57663174N-(2-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,4-difluoro-N-(phenylmethyl)benzenesulfonamide

Product 1

HCID 576632163-{[1,1-dioxido-2-(phenylmethyl)-3,4-dihydro-2H-5,1,2-benzoxathiazepin-7-yl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 117.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

N-(2-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}ethyl)-2,4-difluoro-N-(phenylmethyl)benzenesulfonamide (291 mg, 0.66 mmol) was added to 3-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-{(s)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamide (296 mg, 0.66 mmol) and potassium carbonate (183 mg, 1.31 mmol) in dry DMA (4 mL). The mixture was heated in a Smith Creator microwave at 150° C. for 45 mins. Water (25 mL) was added to the reaction mixture and extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and evaporated. Purification by column chromatography on silica, eluting with 80-90% ethyl acetate in isohexane, afforded the title compound as a colourless oil (450 mg). 1H NMR δ (CDCl3): 1.25 (d, 3H), 2.16-2.19 (m, 1H), 3.53 (t, 2H), 3.68-3.71 (m, 2H), 3.74 (s, 3H), 4.14 (t, 2H), 4.18 (s, 2H), 4.50 (ddd, 1H), 6.70 (d, 1H), 6.72 (d, 1H), 6.75 (t, 1H), 6.78 (dd, 1H), 7.09 (t, 1H), 7.22 (ddd, 1H), 7.24-7.26 (m, 1H), 7.28-7.29 (m, 5H), 7.78 (d, 1H), 8.45 (s, 1H). m/z 579 (M+H)+

Workup

  1. extractionextracted with ethyl acetate (3×30 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customPurification by column chromatography on silica
  6. washeluting with 80-90% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-10be47cb97064eb196c4da7a106d4d31
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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