Water → (11S)-11-Methyl-2-(1,3-thiazol-4-ylmethoxy)-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

HRID 1035569Notes

Reaction equation

HRID 1035569 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]3[CH2:18][O:17][CH2:16][C@H:15]([CH3:19])[N:14]3[C:10]=2[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:20])[CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:29][C:30]1[N:31]=[CH:32][S:33][CH:34]=1.O>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)(Cl)Cl>[CH3:19][C@@H:15]1[N:14]2[C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[C:7]([O:20][CH2:29][C:30]5[N:31]=[CH:32][S:33][CH:34]=5)[CH:8]=4)[N:3]=[C:2]([NH2:1])[C:11]=3[N:12]=[C:13]2[CH2:18][O:17][CH2:16]1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27632894-(Chloromethyl)-1,3-thiazole hydrochlorideHCID 58406167(11S)-6-amino-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-2-ol

Product 1

HCID 58406176(11S)-11-Methyl-2-(1,3-thiazol-4-ylmethoxy)-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amineYield 26.3%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (11S)-6-amino-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-2-ol (500 mg, 1.85 mmol) dissolved in 15 mL of DMF was treated with cesium carbonate (1.80 g, 5.55 mmol), 4-chloromethyl thiazole hydrochloride (345 mg, 2.03 mmol), and tetrabutylammonium bromide (715 mg, 2.22 mmol). After stirring overnight at ambient temperature, the brown mixture was poured into 150 mL of H2O and stirred for 30 minutes. The reaction mixture was extracted with CHCl3 (3×75 mL) and the combined extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give a brown solid. Chromatography (SiO2, 0-20% CMA/CHCl3) gave an off-white solid which was crystallized from acetonitrile to give 179 mg of the title compound as an off-white solid, mp 240-242° C. 1H NMR (500 MHz, DMSO-d6) δ 9.16 (d, J=2.0 Hz, 1H), 7.82 (d, J=1.9 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 7.51 (d, J=2.7 Hz, 1H), 7.21 (dd, J=2.6, 9.1 Hz, 1H), 6.35 (br s, 2H), 5.36 (m, 2H), 5.14 (m, 1H), 5.09 (d, J=15.5 Hz, 1H), 4.95 (d, J=15.5 Hz, 1H), 4.13 (m, 2H), 1.52 (d, J=6.5 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 154.4, 152.8, 152.7, 150.3, 145.0, 139.6, 130.9, 127.3, 126.7, 118.0, 116.9, 114.3, 102.8, 68.2, 65.6, 64.5, 49.8, 18.9; MS (APCI) m/z 368 (M+H)+. Anal. calcd for C18H12N5O2S: C, 58.84; H, 4.66; N, 19.06. Found: C, 58.88; H, 4.63; N, 19.29.

Workup

  1. stirringstirred for 30 minutes
  2. extractionThe reaction mixture was extracted with CHCl3 (3×75 mL)
  3. dry with materialthe combined extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a brown solid
  7. customwas crystallized from acetonitrile

Sources & evidence

ORD record
ord-0650e43d662c40099be64ef7006f02f7
Source dataset
uspto-grants-2013_10
Patent number
US08546383B2

Reaction notes

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