Hydrochloric Acid → HCID 66642954, compound

HRID 869255Notes

Reaction equation

HRID 869255 reaction equation
[NH2:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH2:11][CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)[C:7](=O)[CH2:8][O:9][C:4]=2[CH:3]=1.B.O1CCCC1.Cl.[OH-].[Na+]>O.CO.C1COCC1>[CH3:20][N:17]1[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][N:6]2[C:5]3[CH:21]=[CH:22][C:2]([NH2:1])=[CH:3][C:4]=3[O:9][CH2:8][CH2:7]2)[CH2:15][CH2:16]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 66642955HCID 66642955, compound

Product 1

HCID 66642954HCID 66642954, compoundYield 41.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 7-amino-4-[3-(4-methylpiperazin-1-yl)propyl]-2H-1,4-benzoxazine-3(4H)-one (Preparation Example 435) (300 mg) and THF (9 mL), gradual dropwise addition of borane-tetrahydrofuran complex (3.0 mL, 1M THF solution) was conducted under ice cooling under an argon atmosphere. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour and further stirred at 70° C. for 3 hours. After methanol (10 mL) was gradually added to the reaction liquid under ice cooling, 1M hydrochloric acid (5 mL) and thereafter 1M aqueous sodium hydroxide (10 mL) were added and stirred at room temperature for 1 hour. After dilution with water, the reaction liquid was extracted with ethyl acetate. After the solvent was distilled off, the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1) to give 4-[3-(4-methylpiperazin-1-yl)propyl]-3,4-dihydro-2H-1,4-benzoxazine-7-amine (120 mg).

Workup

  1. additionAfter the dropwise addition
  2. stirringfurther stirred at 70° C. for 3 hours
  3. stirringstirred at room temperature for 1 hour
  4. extractionwas extracted with ethyl acetate
  5. distillationAfter the solvent was distilled off
  6. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1)

Sources & evidence

ORD record
ord-eb7cb4b0858f4bb9ade10cce861658c3
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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