Diisopropylethylamine → HCID 86680131, compound

HRID 1915932Notes

Reaction equation

HRID 1915932 reaction equation
Cl.Cl.[O:3]1[C@@H:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13][C@H:7]2[NH:6][CH2:5][CH2:4]1.Cl[C:15]1[N:19]([CH3:20])[N:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22].CCN(C(C)C)C(C)C>C(#N)C.O>[CH3:20][N:19]1[C:15]([N:11]2[CH2:12][CH2:13][C@@H:7]3[NH:6][CH2:5][CH2:4][O:3][C@H:8]3[CH2:9][CH2:10]2)=[C:16]([N+:21]([O-:23])=[O:22])[CH:17]=[N:18]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 86680132HCID 86680132, compound

Product 1

HCID 86680131HCID 86680131, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a microwave reaction vial, (4aR,9aR)-2,3,4,4a,5,6,7,8,9,9a-decahydro-[1,4]oxazino[2,3-d]azepine dihydrochloride (509 mg; 2.22 mmol) and 5-chloro-1-methyl-4-nitro-pyrazole (322 mg, 2.00 mmol) were dissolved in acetonitrile (16 mL). DIPEA (3.11 mL, 17.77 mmol) was added and the mixture was irradiated with microwave at 130° C. for 60 min. The reaction mixture was diluted with water, extracted with EA 3×. Combined organic layers were dried over Na2SO4 and concentrated to give trans-7-(2-methyl-4-nitro-pyrazol-3-yl)-3,4,4a,5,6,8,9,9a-octahydro-2H-[1,4]oxazino[2,3-d]azepine. To a solution of this compound in DCM (15 mL) was added di-tert-butyl-dicarbonate (727 mg, 3.33 mmol) and DIPEA (1.16 mL, 6.66 mmol). The mixture was stirred at room temperature for 18 h. The crude reaction mixture was concentrated and the residue was purified via silica gel column chromatography (0-100% EA/heptane) to gave the racemic trans-tert-butyl-7-(2-methyl-4-nitro-pyrazol-3-yl)-2,3,4a,5,6,8,9,9a-octahydro-[1,4]oxazino[2,3-d]azepine-4-carboxylate, which was chirally separated on AD column with 20% methanol w/0.1% NH4OH. The first eluting peak of trans-tert-butyl-7-(2-methyl-4-nitro-pyrazol-3-yl)-2,3,4a,5,6,8,9,9a-octahydro-[1,4]oxazino[2,3-d]azepine-4-carboxylate off the SFC chiral separation was converted to 396 following the procedures of Example 354. 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 7.55 (s, 1H), 7.54-7.43 (m, 3H), 7.26 (t, J=8.7 Hz, 2H), 3.64 (s, 3H), 3.24-3.13 (m, 4H), 3.13-2.95 (m, 3H), 2.65 (d, J=5.6 Hz, 2H), 2.60-2.52 (m, 1H), 1.82-1.68 (m, 3H), 1.64-1.53 (m, 2H). LCMS (ES+) m/z 490 (M+1)

Workup

  1. customIn a microwave reaction vial
  2. customthe mixture was irradiated with microwave at 130° C. for 60 min
  3. extractionextracted with EA 3×
  4. dry with materialCombined organic layers were dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-50d5024066b447bdb01aabc51709b3c0
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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