tert-Butyl ethyl(2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamate → tert-Butyl ethyl(2-(7-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamate

HRID 424480Notes

Reaction equation

HRID 424480 reaction equation
[CH2:1]([N:3]([CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[C:20]([N+:23]([O-])=O)[CH:21]=[CH:22][C:14]1=2)[C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7])[CH3:2].I.[S:27]1[CH:31]=[CH:30][CH:29]=[C:28]1[C:32](SC)=[NH:33]>CCO.[Pd]>[CH2:1]([N:3]([CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][O:16][C:15]2[CH:19]=[C:20]([NH:23][C:32]([C:28]3[S:27][CH:31]=[CH:30][CH:29]=3)=[NH:33])[CH:21]=[CH:22][C:14]1=2)[C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7])[CH3:2]

Participants

5

Reactant 2

HCID 59144101tert-Butyl ethyl(2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamateHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178464390tert-Butyl ethyl(2-(7-(thiophene-2-carboximidamido)-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamateYield 46.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A suspension of tert-butyl ethyl(2-(7-nitro-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)carbamate (7 g, 19.92 mmol) and Pd—C (2.11 g, 1.992 mmol, 10% wt) in anhydrous EtOH (100 mL) was purged with hydrogen gas. The reaction was stirred at room temperature for 16 hours under a hydrogen atmosphere (balloon pressure). The reaction mixture was filtered through a Celite pad and washed with EtOH (50 mL). The filtrate containing tert-butyl 2-(7-amino-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl(ethyl)carbamate was treated with methyl thiophene-2-carbimidothioate hydroiodide (11.36 g, 39.8 mmol) and stirred overnight at room temperature. The reaction was concentrated and then partitioned between saturated NaHCO3 solution (150 mL) and CH2Cl2 (75 mL). The mixture was transferred to a separatory funnel, and the product was extracted into CH2Cl2 (2×100 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was subjected to flash chromatography on silica gel using a sequence of eluents (CH2Cl2; 1:99 (2M NH3 in MeOH):CH2Cl2; 1.75:98.25 (2M NH3 in MeOH):CH2Cl2; and 2.5:97.5 (2M NH3 in MeOH):CH2Cl2) to give a brown solid (4 g, 46.7%). 1H-NMR (CDCl3) δ 7.43-7.41 (m, 2H), 7.11-7.05 (m, 1H), 6.72-6.69 (m, 1H), 6.54-6.51 (m, 2H), 4.23-4.20 (m, 2H), 3.39-3.25 (m, 8H), 1.47 (s, 9H), 1.11-1.10 (m, 3H); ESI-MS (m/z, %): 431 (MH+, 100).

Workup

  1. customwas purged with hydrogen gas
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with EtOH (50 mL)
  4. additionThe filtrate containing tert-butyl 2-(7-amino-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl(ethyl)carbamate
  5. stirringstirred overnight at room temperature
  6. concentrationThe reaction was concentrated
  7. custompartitioned between saturated NaHCO3 solution (150 mL) and CH2Cl2 (75 mL)
  8. customThe mixture was transferred to a separatory funnel
  9. extractionthe product was extracted into CH2Cl2 (2×100 mL)
  10. dry with materialThe combined organic layers were dried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-8fa092e1c81b41aca95c6b0890e3f696
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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