Water → HCID 86680001, compound

HRID 1915789Notes

Reaction equation

HRID 1915789 reaction equation
[N:1]([CH:4]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:7][CH2:6][CH:5]1[OH:20])=[N+:2]=[N-:3].[H-].[Na+].I[CH3:24].O>CN(C=O)C>[N:1]([CH:4]1[CH:5]([O:20][CH3:24])[CH2:6][CH2:7][N:8]([C:11]2[N:15]([CH3:16])[N:14]=[CH:13][C:12]=2[N+:17]([O-:19])=[O:18])[CH2:9][CH2:10]1)=[N+:2]=[N-:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86679998HCID 86679998, compound

Product 1

HCID 86680001HCID 86680001, compoundYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol (420 mg, 1.49 mmol) in dry DMF (15 mL) cooled to 0° C. was added sodium hydride (60% in mineral oil, 90 mg, 2.24 mmol). After stirring for 15 min, iodomethane (0.14 mL, 2.24 mmol) was added and the reaction mixture was allowed to warm to room temperature and stirred for 1 hr. Water (20 mL) was added and the mixture was extracted with EtOAc (150 mL). The organic layer was washed with water (6×30 mL) and brine (20 mL), separated, dried over MgSO4, and concentrated under reduced pressure. Purification via silica gel column chromatography gave 4-azido-5-methoxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as a yellow oil (350 mg). A solution of this oil (350 mg, 1.19 mmol) in THF/water (15 mL/3 mL) was treated with triphenylphosphine (311 mg, 1.19 mmol) and the reaction mixture was heated at 60° C. behind a blast screen for 18 hr. Water (2 mL) was added and the mixture was extracted with EtOAc (2×50 mL) The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The resulting oil was triturated in Et2O, the resulting solid was filtered off and the filtrate concentrated under reduced pressure to give a yellow oil. To a solution of this oil (319 mg, 1.19 mmol) in dry DCM (10 mL) at 0° C. was added a solution of di-tert-butyl-dicarbonate (310 mg, 1.42 mmol) in DCM (10 mL) and DIPEA (1.0 mL, 5.93 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 72 hr. Water (20 mL) was added and the mixture extracted with DCM (100 mL). The organic layer was separated, dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (40-50% EtOAc/isohexane) gave tert-butyl 5-methoxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate as a yellow oil (355 mg, 64% over three steps). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 5.14 (d, J=8.9 Hz, 1H), 4.00-3.90 (m, 1H), 3.78 (s, 3H), 3.68-3.60 (m, 1H), 3.48 (t, J=12.6 Hz, 1H), 3.39 (s, 3H), 3.33-3.23 (m, 1H), 3.19-3.11 (m, 1H), 3.04-2.95 (m, 1H), 2.25-2.06 (m, 2H), 1.88-1.76 (m, 2H), 1.45 (s, 9H).

Workup

  1. stirringstirred for 1 hr
  2. extractionthe mixture was extracted with EtOAc (150 mL)
  3. washThe organic layer was washed with water (6×30 mL) and brine (20 mL)
  4. customseparated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification via silica gel column chromatography

Sources & evidence

ORD record
ord-f66cceeeecea4fb2a69f3c05fcfbe5cb
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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