Chloroform → HCID 68539394, compound

HRID 1992523Notes

Reaction equation

HRID 1992523 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH2:17][CH2:16][CH:15]([NH:18][CH2:19][CH2:20][NH2:21])[CH2:14]1.[O:22]=[C:23]1[CH2:28][O:27][C:26]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[N:32][C:25]=2[NH:24]1.[BH4-].[Na+].C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:43]>CO.C(Cl)Cl>[ClH:43].[ClH:43].[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH2:17][CH2:16][CH:15]([NH:18][CH2:19][CH2:20][NH:21][CH2:33][C:31]2[CH:30]=[CH:29][C:26]3[O:27][CH2:28][C:23](=[O:22])[NH:24][C:25]=3[N:32]=2)[CH2:14]1

Participants

8

Reactant 5

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 58955137HCID 58955137, compound

Product 1

HCID 68539394HCID 68539394, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

N1-[1-(6-Methoxy-[1,5]naphthyridin-4-yl)-pyrrolidin-3-yl]-ethane-1,2-diamine (250 mg, 0.77 mmol) (from Example 2c) was dissolved in MeOH:DCM (8 mL, 1:1) and treated with 3-oxo-3,4-dihydro-2H -pyrido[3,2-b ][1,4]oxazine-6-carbaldehyde (138 mg, 0.77 mmol). After stirring overnight, the reaction mixture was treated with sodium borohydride (29 mg, 0.77 mmol) and stirred 1 h. The reaction mixture was diluted with chloroform and poured into saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted several times with chloroform. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated to dryness and purified by colume chromatography (silica, 0-10% MeOH in CDCl3 (1% NH4OH)) to afford the title compound as a white solid (140 mg, 40%): LC/MS m/z 450 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 8.34 (d, J=5 Hz, 1H), 8.07 (d, J=9 Hz, 1H), 7.17 (d, J=8 Hz, 1H), 7.01 (d, J=9 Hz, 1H), 6.88 (d, J=8 Hz, 1H), 6.40 (d, J=5 Hz, 1H), 4.62 (s, 2H), 4.15 (m, 1H), 4.05 (m, 1H), 3.99 (s, 3H), 3.95 (m, 1H), 3.77 (s, 3H), 3.47 (m, 1H), 2.82 (m, 2H), 2.80 (s, 2H), 2.20 (m, 1H), 1.92 (m, 1H).

Workup

  1. stirringstirred 1 h
  2. extractionThe aqueous layer was extracted several times with chloroform
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. custompurified by colume chromatography (silica, 0-10% MeOH in CDCl3 (1% NH4OH))

Sources & evidence

ORD record
ord-c74a70358b4b41eab28eb36d26ffa64e
Source dataset
uspto-grants-2010_01
Patent number
US07648984B2

Reaction notes

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