Water → HCID 178463984, compound

HRID 704250Notes

Reaction equation

HRID 704250 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH2:11]([N:13]([CH2:35][CH3:36])[CH2:14][CH:15]([N:17]1[C:30]2[CH:29]=[C:28]([C:31](=[NH:34])OC)[CH:27]=[CH:26][C:25]=2[S:24][C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16])[CH3:12].O>CO>[CH2:1]([NH:8][C:31]([C:28]1[CH:27]=[CH:26][C:25]2[S:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([CH:15]([CH3:16])[CH2:14][N:13]([CH2:35][CH3:36])[CH2:11][CH3:12])[C:30]=2[CH:29]=1)=[NH:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 7504BenzylamineHCID 15925386methyl 10-[(2RS)-1-diethylamino-2-propyl]-2-phenothiazinecarboximidate dihydrochloride

Product 1

HCID 178463984HCID 178463984, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of benzylamine (3.18 cc) in methanol (5 cc) is added dropwise in the course of 5 minutes to a solution, cooled to 0°-5° C., of methyl 10-[(2RS)-1-diethylamino-2-propyl]-2-phenothiazinecarboximidate dihydrochloride (3.49 g) in methanol (21 cc). The mixture is stirred for 2 hours at 5° C. and is then concentrated to dryness at 50° C. under reduced pressure (30 mm Hg; 4 kPa) to give a residue which is taken up with distilled water (50 cc). The solution is washed with distilled water (50 cc) alkalinized to a pH in the region of 9 with N sodium hydroxide. The two phases are allowed to settle and the organic phase is separated and washed with half-saturated sodium chloride solution (50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The residue is purified by chromatography on a column of neutral alumina (height: 24 cm; diameter: 2.1 cm), eluting successively with mixtures of cyclohexane and ethyl acetate in proportions of 50:50 (500 cc) and 25:75 (500 cc), then with pure ethyl acetate (500 cc) and finally with mixtures of ethyl acetate and methanol in proportions of 95:5 (500 cc) and 90:10 (500 cc) and collecting 50-cc fractions. Fractions 35 to 53 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. to give N-benzyl-10-[ (2RS)-1-diethylamino-2-propyl]-2-phenothiazinecarboxamidine (0.96 g) in the form of a yellow product of meringue-like consistency.

Workup

  1. concentrationis then concentrated to dryness at 50° C. under reduced pressure (30 mm Hg; 4 kPa)
  2. customto give a residue which
  3. washThe solution is washed with distilled water (50 cc)
  4. customthe organic phase is separated
  5. washwashed with half-saturated sodium chloride solution (50 cc)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C
  9. customThe residue is purified by chromatography on a column of neutral alumina (height: 24 cm; diameter: 2.1 cm)
  10. washeluting successively with mixtures of cyclohexane and ethyl acetate in proportions of 50:50 (500 cc) and 25:75 (500 cc)
  11. customwith pure ethyl acetate (500 cc) and finally with mixtures of ethyl acetate and methanol in proportions of 95:5 (500 cc) and 90:10 (500 cc) and collecting 50-cc fractions
  12. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C.

Sources & evidence

ORD record
ord-3f684aeb2d2446699ae9d25c2ccffeaa
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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