Triphenylphosphine → HCID 89456414, compound

HRID 1915794Notes

Reaction equation

HRID 1915794 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][CH:6]([O:20][CH3:21])[CH2:5]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[CH3:21][O:20][CH:6]1[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][CH:4]([NH2:1])[CH2:5]1

Participants

5

Reactant 2

HCID 11776TriphenylphosphineHCID 86680004HCID 86680004, compound

Product 1

HCID 89456414HCID 89456414, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-3-ol, Intermediate 18 (0.85 g, 3.0 mmol) in DMF (5 mL) cooled to 0° C. under nitrogen, was added sodium hydride (60% in mineral oil, 133 mg, 3.3 mmol) and the resulting mixture was stirred for 10 min. Iodomethane (0.37 mL, 6.0 mmol) was added and the mixture stirred at room temperature for 16 hr. Water (200 mL) was added and the mixture extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-50% EtOAc/isohexane) gave 5-azido-3-methoxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as an oil (0.76 g). This azide (0.76 g, 2.6 mmol) in THF (15 mL) and water (3 mL) was treated with triphenylphosphine (0.71 g, 2.7 mmol). The mixture was heated at 65° C. for 16 hr and the solvents were removed under reduced pressure to afford 6-methoxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-amine. This amine was suspended in DCM (40 mL) and di-tert-butyl dicarbonate (1.13 g, 5.2 mmol) and DIPEA (1.36 mL, 7.8 mmol) were added. After stirring at room temperature for 16 hr the solvent was removed under reduced pressure and the residue dissolved in DCM (40 mL). Water (20 ml) was added and the organic layer was separated, dried over Na2SO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (0-50% EtOAc/isohexane) gave tert-butyl 6-methoxy-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ylcarbamate (0.84 g, 74% over three steps) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J=4.3 Hz, 1H), 5.39 (d, J=7.9 Hz, 1H), 4.21-3.94 (m, 1H), 3.84 (s, 3H), 3.56-3.42 (m, 2H), 3.35-3.03 (m, 6H), 2.28-1.89 (m, 4H), 1.46 (s, 9H).

Workup

  1. customthe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-d0bfe3912f0342b6b9c609139242fc56
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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