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

HRID 221612Notes

Reaction equation

HRID 221612 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]=[C:32]([CH3:35])[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]=[C:32]([CH3:35])[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 27342034-(Chloromethyl)-2-methyl-1,3-thiazole--hydrogen chloride (1/1)HCID 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 58406164(11S)-11-Methyl-2-[(2-methyl-1,3-thiazol-4-yl)methoxy]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amineYield 33.6%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

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-2-methylthiazole hydrochloride (375 mg, 2.03 mmol) and tetrabutylammonium bromide (715 mg, 2.22 mmol). After stirring overnight at 50° C., the dark 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 237 mg of the title compound as an off-white solid, mp 105-107° C. 1H NMR (500 MHz, DMSO-d6) δ 7.59 (s, 1H), 7.57 (s, 1H), 7.51 (d, J=2.7 Hz, 1H), 7.19 (dd, J=2.7, 9.1 Hz, 1H), 6.35 (br s, 2H), 5.25 (m, 2H), 5.14 (m, 1H), 5.09 (d, J=15.5 Hz, 1H), 4.95 (d, J=15.5 Hz, 1H), 4.14 (m, 2H), 2.67 (s, 3H), 1.54 (d, J=6.5 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 165.6, 152.7, 151.5, 150.3, 145.0, 139.6, 130.9, 127.4, 126.7, 117.6, 116.9, 114.3, 102.8, 68.2, 65.6, 64.6, 49.8, 19.0, 18.6; MS (APCI) m/z 382 (M+H)+. Anal. calcd for Cl9H19N5O2.0.75 C4H8O2.0.33H2O: C, 58.88; H, 5.28; N, 19.26. Found: C, 58.62; H, 4.96; N, 19.10.

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-252241fc36104d26ab29bb45d3c20ed4
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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