Water → HCID 86679997, compound

HRID 1915786Notes

Reaction equation

HRID 1915786 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].C(N(CC)CC)C.[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1.O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([O:20][CH:5]2[CH:4]([N:1]=[N+:2]=[N-:3])[CH2:10][CH2:9][N:8]([C:11]3[N:15]([CH3:16])[N:14]=[CH:13][C:12]=3[N+:17]([O-:19])=[O:18])[CH2:7][CH2:6]2)(=[O:37])=[O:36])=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chloride2×HCID 8471TriethylamineHCID 86679998HCID 86679998, compound

Product 1

HCID 86679997HCID 86679997, compoundYield 45.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-ol (4.0 g, 14.2 mmol) in dry DCM (100 mL) cooled to 0° C. was added slowly triethylamine (4.0 mL, 28.5 mmol) followed by DMAP (175 mg, 1.42 mmol) and 4-methylbenzene-1-sulfonyl chloride (4.1 g, 21.4 mmol) portionwise. The reaction mixture was allowed to warm to room temperature and stirred for 18 hr. More 4-methylbenzene-1-sulfonyl chloride (1.4 g, 7.12 mmol) was added to the reaction mixture, which was stirred at room temperature for a further 24 hr. Water (40 mL) was added and the mixture was extracted with DCM (100 mL). The organic layer was separated, dried over MgSO4 and the solvent removed under reduced pressure. Purification via silica gel column chromatography (30-70% EtOAc/isohexane) gave 5-azido-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl 4-methylbenzenesulfonate as a dark cream solid (2.81 g). This solid (2.3 g, 5.29 mmol) was treated with a solution of TBAF (1.0 M in THF, 21 mL, 21.1 mmol) and the reaction mixture was heated at 60° C. for 2 hr. After cooling to room temperature, water (30 mL) was added and the mixture was extracted with EtOAc (2×150 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (30-40% EtOAc/isohexane) gave 4-azido-5-fluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as a yellow viscous oil (804 mg, 20% over two steps) 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 5.06 (ddt, J=46.2, 8.1, 2.5 Hz, 1H), 4.00 (dd, J=20.8, 8.1 Hz, 1H), 3.79 (s, 3H), 3.43-3.34 (m, 2H), 3.26-3.11 (m, 2H), 2.43-2.30 (m, 1H), 2.30-2.18 (m, 1H), 2.12-1.92 (m, 2H).

Workup

  1. stirringwas stirred at room temperature for a further 24 hr
  2. extractionthe mixture was extracted with DCM (100 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. customthe solvent removed under reduced pressure
  6. customPurification via silica gel column chromatography (30-70% EtOAc/isohexane)

Sources & evidence

ORD record
ord-f7f827e03d4a4df7850699de8c7b88d5
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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