7-Nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine → HCID 178511895, compound

HRID 424470Notes

Reaction equation

HRID 424470 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]([CH2:13][CH2:14][N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[CH2:11][CH2:10][O:9][C:8]=2[CH:20]=1)([O-])=O.I.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:27](SC)=[NH:28]>CCO.C([O-])(O)=O.[Na+].[Pd]>[N:15]1([CH2:14][CH2:13][N:12]2[CH2:11][CH2:10][O:9][C:8]3[CH:20]=[C:4]([NH:1][C:27]([C:23]4[S:22][CH:26]=[CH:25][CH:24]=4)=[NH:28])[CH:5]=[CH:6][C:7]2=3)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 2

HCID 578702597-Nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511895HCID 178511895, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A suspension of 7-nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (330 mg, 1.190 mmol) and Pd—C (252 mg, 0.238 mmol, 10% wt) in dry EtOH (10 mL) was purged with hydrogen gas. The reaction was stirred at room temperature for 1.5 hours under a hydrogen atmosphere (balloon pressure). The reaction mixture was filtered through a Celite pad and washed with EtOH (25 mL). The filtrate was treated with methyl thiophene-2-carbimidothioate hydroiodide (0.678 g, 2.377 mmol) and stirred for three days at room temperature. The reaction was diluted with saturated NaHCO3 solution (50 mL), and the product was extracted into CH2Cl2 (3×25 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was subjected to flash chromatography on silica gel using 2:98 MeOH:CH2Cl2 followed by 5:95 (2M NH3 in MeOH):CH2Cl2 to give a yellow solid (150 mg, 36%). 1H-NMR (DMSO-d6) δ 7.70 (d, J=3.6 Hz, 1H), 7.57 (dd, J=5.1, 0.9 Hz, 1H), 7.08 (dd, J=5.1, 3.9 Hz, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.34 (dd, J=2.4, 8.4 Hz, 1H), 6.252 (d, J=2.4, 1H), 6.36-6.25 (m, 2H), 4.15 (t, J=4.2 Hz, 2H), 3.38-3.30 (m, 4H), 2.64 (t, J=7.2 Hz, 2H), 2.58-2.48 (m, 4H), 1.70-1.67 (m, 4H); ESI-MS (m/z, %): 357 (MH+, 100), 260 (40), 98 (27); ESI-HRMS calculated for C19H25N4OS (MH+): 357.1743, observed: 357.1734; HPLC purity: 95.8% by area.

Workup

  1. customwas purged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with EtOH (25 mL)
  4. stirringstirred for three days at room temperature
  5. extractionthe product was extracted into CH2Cl2 (3×25 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e287ed5c50264541a272aa410a851d7b
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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