Water → HCID 86615674, compound

HRID 2261891Notes

Reaction equation

HRID 2261891 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([N:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:21][CH2:22][CH3:23])[CH:19]=1)[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])=[O:6].O.N([O-])=O.[Na+].[N-:33]=[N+:34]=[N-].[Na+]>C(O)(=O)C.CCOC(C)=O>[N:1]([C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([N:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:21][CH2:22][CH3:23])[CH:19]=1)[C:5]([NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])=[O:6])=[N+:33]=[N-:34]

Participants

7

Reactant 4

HCID 962WaterHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 58990135HCID 58990135, compound2×

Product 1

HCID 86615674HCID 86615674, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.2 g (0.5 mmol) 3-amino-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide (Intermediate XXI) in 4 mL acetic acid was added 1 mL water followed by 0.038 g (0.55 mmol) sodium nitrite. After 2 minutes 0.035 g (0.055 mmol) sodium azide was added resulting in gas evolution. The reaction mixture was stirred for 30 minutes then diluted with 75 mL EtOAc, washed with 50 mL water, 50 mL 4M NaOH, 50 mL brine, dried over MgSO4, filtered, and concentrated. Purification by automated flash chromatography (40 g silica gel cartridge, 20-100% EtOAc/hexanes over 20 min) afforded 3-azido-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide. 1H NMR (CDCl3, 400 MHz) δ 7.45 (br t, J=1.47 Hz, 1H), 7.36 (m, 3H), 7.11 (t, J=2.01 Hz, 1H), 7.06 (m, 2H), 6.31 (br d, J=7.32 Hz, 1H), 5.28 (quint, J=7.14 Hz, 1H), 3.64 (t, J=7.15 Hz, 2H), 2.89 (s, 3H), 1.61 (d, J=6.96 Hz, 3H), 1.5 (m, 2H), 0.91 (t, J=7.33 Hz, 3H). LCMS [M+H]+=420.1

Workup

  1. customresulting in gas evolution
  2. washwashed with 50 mL water, 50 mL 4M NaOH, 50 mL brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by automated flash chromatography (40 g silica gel cartridge, 20-100% EtOAc/hexanes over 20 min)

Sources & evidence

ORD record
ord-d20b49dff91c4afc8fa90612989fe4b1
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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