Benzyl Alcohol → HCID 21219108, compound

HRID 1585654Notes

Reaction equation

HRID 1585654 reaction equation
Cl[C:2]([O:5][C:6](Cl)=[O:7])(Cl)Cl.[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([NH:19][C:20]2[N:21]=[C:22]([C:30]3[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]=3)[CH:23]=[C:24]3[C:29]=2[N:28]=[CH:27][CH:26]=[CH:25]3)(=[O:18])=[O:17])=[CH:12][CH:11]=1.C([N:39]([CH2:42]C)CC)C.[Li].C([OH:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CN(C)C1C=CN=CC=1.ClCCl.O1CCCC1>[CH3:36][C:35]1[C:30]([C:22]2[CH:23]=[C:24]3[C:29](=[C:20]([NH:19][S:16]([C:13]4[CH:14]=[CH:15][C:10]([NH:9][C:6](=[O:7])[O:5][CH2:2][C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)=[CH:11][CH:12]=4)(=[O:18])=[O:17])[N:21]=2)[N:28]=[CH:27][CH:26]=[CH:25]3)=[N:31][CH:32]=[CH:33][CH:34]=1.[NH2:39][C:42]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([NH:19][C:20]2[N:21]=[C:22]([C:30]3[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][N:31]=3)[CH:23]=[C:24]3[C:29]=2[N:28]=[CH:27][CH:26]=[CH:25]3)(=[O:18])=[O:17])=[CH:12][CH:11]=1)=[O:52]

Participants

11

Reactant 6

HCID 244Benzyl Alcohol4×HCID 8471TriethylamineHCID 10426DiphosgeneHCID 2733832Lithium Hexamethyldisilazide2×HCID 3028194Lithium2×HCID 21219087HCID 21219087, compound

Product 2

HCID 21219108HCID 21219108, compoundHCID 54560761HCID 54560761, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

Rapidly add trichloromethylchloroformate (0.16 mL, 1.32 mmol) to a stirred suspension of 8-(p-aminobenzenesulfonamido)-6-(3-methyl-2-pyridinyl)-1,7-naphthyridine (0.43 g, 1.10 mmol), triethylamine (0.183 mL, 1.32 mmol) and 4-dimethylaminopyridine (0.03 g) in dichloromethane (25 mL) at 25° C. Stir for 1 hour at room temperature. Add this reaction mixture to a stirred solution of the lithium salt of benzyl alcohol [prepared by stirring a 1M solution (1.5 mL, 1.5 mmol) of lithium bis(trimethylsilyl)amide in tetrahydrofuran with benzyl alcohol (0.15 mL, 1.45 mmol) in dichloromethane (20 mL) for 0.5 hour]. Stir the resultant mixture for 3 days at room temperature. Introduce additional lithium salt of benzyl alcohol [prepared as described above from a 1M solution (3 mL, 3 mmol) of lithium bis(trimethylsilyl)amide in tetrahydrofuran with benzyl alcohol (0.30 mL, 2.90 mmol) in dichloromethane (1 mL)] and reflux for 24 hours. Remove solvent under reduced pressure, and flash chromatograph on a column of silica gel, eluting with a stepped gradient of dichloromethane-methanol-ammonium hydroxide (95:5:0.1→90:9:0.1) to obtain the title compounds I and II. Reflux the less polar solid thus isolated in methanol-ethanol (1:1) for 5-10 minutes, cool to room temperature, and filter to obtain title compound I as a 0.25 hydrate, C28H23N5O4S.0.25 H2O, mp 229.5-231° C. (dec). FABMS: MH+ 526 (100%). Crystallize from ethanol (5 mL) the more polar solid eluted from the column to obtain title compound II as a 0.5 hydrate, C21H18N6O3S.0.5 H2O, mp 258.5-260° C. (dec). FABMS: MH+ 435 (94%).

Workup

  1. customprepared
  2. customprepared
  3. temperaturereflux for 24 hours
  4. washRemove solvent under reduced pressure, and flash chromatograph on a column of silica gel, eluting with a stepped gradient of dichloromethane-methanol-ammonium hydroxide (95:5:0.1→90:9:0.1)

Sources & evidence

ORD record
ord-8186533fc54049f9bcc566c8ad51c38f
Source dataset
uspto-grants-1999_08
Patent number
US05939431

Reaction notes

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