6-Nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine → HCID 178511893, compound

HRID 1917217Notes

Reaction equation

HRID 1917217 reaction equation
[N+:1]([C:4]1[CH:20]=[CH:19][C:7]2[S:8][CH2:9][CH2:10][N:11]([CH2:12][CH2:13][N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[CH:5]=1)([O-])=O.I.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:27](SC)=[NH:28]>C(O)C.ClCCl.[Pd]>[N:14]1([CH2:13][CH2:12][N:11]2[CH2:10][CH2:9][S:8][C:7]3[CH:19]=[CH:20][C:4]([NH:1][C:27]([C:23]4[S:22][CH:26]=[CH:25][CH:24]=4)=[NH:28])=[CH:5][C:6]2=3)[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

6

Reactant 2

HCID 591440686-Nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazineHCID 66704664Methyl thiophene-2-carbimidothioate hydroiodide

Product 1

HCID 178511893HCID 178511893, compoundYield 53.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 6-nitro-4-(2-(pyrrolidin-1-yl)ethyl)-3,4-dihydro-2H-benzo[b][1,4]thiazine (649 mg, 2.212 mmol) in ethanol (5 mL) was added palladium, 10 wt. % on activated carbon (235 mg, 0.221 mmol) as a suspension in ethanol (5 mL). The resulting suspension was stirred under an atmosphere of hydrogen (balloon pressure) for 3 hours (yellow color disappears). The balloon was removed, and methyl thiophene-2-carbimidothioate hydroiodide (1.262 g, 4.42 mmol) was added to the mixture. The resulting mixture was stirred under argon overnight at room temperature. The mixture was then diluted with dichloromethane and filtered through Celite. The filtrate was then diluted with saturated sodium carbonate and extracted with dichloromethane (2×). The combined organics were dried, filtered, concentrated, and then chromatographed in 1:19 (2M NH3 in methanol):ethyl acetate, giving the desired product 25 (438 mg, 53.1%). 1H NMR (DMSO-d6) δ 7.71 (d, J=3.3 Hz, 1H), 7.58 (d, J=5.1 Hz, 1H), 7.10-7.06 (m, 1H), 6.83 (d, J=8.1 Hz, 1H), 6.38 (brs, 2H), 6.19 (s, 1H), 6.08 (d, J=1H), 3.63-3.58 (m, 2H), 3.40-3.33 (m, 2H), 3.01-2.97 (m, 2H), 2.61 (t, J=6.8 Hz, 2H), 2.49-2.42 (m, 4H), 1.70-1.61 (m, 4H); ESI-MS (m/z, %): 373 (MH+, 62), 276 (100); HRMS calculated for C19H25N4S2 (MH+), calculated: 373.1515, observed: 373.1512; HPLC purity: 97% by area.

Workup

  1. customThe balloon was removed
  2. stirringThe resulting mixture was stirred under argon overnight at room temperature
  3. filtrationfiltered through Celite
  4. additionThe filtrate was then diluted with saturated sodium carbonate
  5. extractionextracted with dichloromethane (2×)
  6. customThe combined organics were dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed in 1:19 (2M NH3 in methanol)

Sources & evidence

ORD record
ord-9d7f8979732046559f49eb7bdb7ec915
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

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