Water → HCID 69654978, compound

HRID 1794909Notes

Reaction equation

HRID 1794909 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][S:15]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)(=[O:17])=[O:16])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[NH2:24][CH2:25][C@@H:26]([C:28]1[CH:29]=[CH:30][C:31]([OH:39])=[C:32]([NH:34][S:35]([CH3:38])(=[O:37])=[O:36])[CH:33]=1)[OH:27].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>CN(C)C=O>[OH:27][C@H:26]([C:28]1[CH:29]=[CH:30][C:31]([OH:39])=[C:32]([NH:34][S:35]([CH3:38])(=[O:37])=[O:36])[CH:33]=1)[CH2:25][NH:24][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH:14][S:15]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)(=[O:17])=[O:16])=[CH:12][CH:13]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 22220427HCID 22220427, compound

Product 1

HCID 69654978HCID 69654978, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of pyridine-3-sulfonic acid-[4-(4-oxo piperidin-1-yl)-phenyl]amide (which was obtained in Example 237) (0.94 g, 2.8 mmol), N-[5-((1R)-2-amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) (0.70 g, 2.8 mmol) in dimethylformamide (10 mL) at room temperature was added sodium triacetoxyborohydride (0.72 g, 3.4 mmol) and glacial acid (0.18 mL, 3.1 mmol). The reaction was stirred under N2 atmosphere for 18 hours. The reaction mixture was poured onto 1:1 water/saturated sodium bicarbonate, extracted with ethyl acetate three times, dried over sodium sulfate and concentrated. The product was purified by flash silica gel chromatography eluting with 10% methanol in methylene chloride and finally with 20% methanol in methylene chloride to give the titled compound as a yellow solid (0.23 g, 15%); 1H NMR (300 MHz, DMSO-d6) δ 1.25–1.45 (m, 2 H), 1.80–1.95(m, 2 H), 2.50–2.80(m, 5 H), 2.92(s, 3 H), 3.40–3.55(m, 2), 4.45–4.60(m, 1 H), 6.85–6.90(m, 5 H), 7.02(dd, J=8.3, 2.0 Hz, 1 H), 7.18(d, J=2.0 Hz, 1 H), 7.59(dd, J=7.4, 4.4 Hz, 1 H), 7.95–8.05(m, 2 H), 8.70–8.80(m, 2 H); MS (ES) m/z: 561.95 (MH+, 100%); HRMS Calcd. for C25H32N5O6S2(MH+): 562.1788. Found: 562.1774.

Workup

  1. extractionextracted with ethyl acetate three times
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customThe product was purified by flash silica gel chromatography
  5. washeluting with 10% methanol in methylene chloride and finally with 20% methanol in methylene chloride

Sources & evidence

ORD record
ord-5955a6b7a0eb4559979e6b78fb09b8cf
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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