Hydrochloric Acid → 3-[7-(azidomethyl)-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

HRID 601343Notes

Reaction equation

HRID 601343 reaction equation
[CH:1]1([CH2:4][NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[C:8]([C:17]3[NH:22][C:21]4[S:23][CH:24]=[C:25]([CH2:26]OCOC)[C:20]=4[S:19](=[O:32])(=[O:31])[N:18]=3)[C:7]2=[O:33])[CH2:3][CH2:2]1.Cl.N12CCCN=C1CCCCC2.C1(P([N:60]=[N+:61]=[N-:62])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCOCC1>[N:60]([CH2:26][C:25]1[C:20]2[S:19](=[O:31])(=[O:32])[N:18]=[C:17]([C:8]3[C:7](=[O:33])[N:6]([NH:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)[C:15]4[C:10]([C:9]=3[OH:16])=[CH:11][CH:12]=[CH:13][CH:14]=4)[NH:22][C:21]=2[S:23][CH:24]=1)=[N+:61]=[N-:62]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 1359745791-[(Cyclopropylmethyl)amino]-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1h)-one

Product 1

HCID 1363584143-[7-(azidomethyl)-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-oneYield 97.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To the product of Example 353C (384.7 mg, 0.78 mmol) was added a solution of hydrogen chloride in dioxane (4N, 7.8 mL) at 0° C. The solution warmed to room temperature and stirred for 5.5 hours and concentrated under reduced pressure. This solid was suspended in dichloromethane (7.8 mL) and to the suspension was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.6 mL, 4.01 mmol) and diphenylphosphoryl azide (0.85 mL, 3.94 mmol) at room temperature and stirred overnight. The solution was concentrated in vacuo. The residue was purified by chromatography, eluting with 1% triethylamine/dichloromethane to give a triethylamine salt of the title compound (357 mg, 79%). MS (ESI−) m/z 470 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.22 (m, 2 H) 0.46 (br d, J=7.35 Hz, 2 H) 1.01 (m, 1 H) 4.52 (s, 2 H) 5.98 (t, J=6.62 Hz, 1 H) 7.24 (s, 1 H) 7.40 (m, 1 H) 7.56 (m, 1 H) 8.05 (m, 1 H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. stirringstirred overnight
  3. concentrationThe solution was concentrated in vacuo
  4. customThe residue was purified by chromatography
  5. washeluting with 1% triethylamine/dichloromethane

Sources & evidence

ORD record
ord-9f1c8b7b15f641d0a97fbc2f6b906628
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

Loading…