Hydrochloric Acid → 2-{5-Chloro-2-[2-(1-methylpiperidin-4-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid amide di-hydrochloride

HRID 1986308Notes

Reaction equation

HRID 1986308 reaction equation
[CH2:1]=O.[Cl:3][C:4]1[C:5]([C:19]2[S:23][C:22]3[CH:24]=[CH:25][CH:26]=[C:27]([C:28]([NH2:30])=[O:29])[C:21]=3[CH:20]=2)=[N:6][C:7]([NH:10][CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[N:8][CH:9]=1.[BH4-].[Na+].[ClH:33]>CO.ClCCl>[ClH:3].[ClH:33].[Cl:3][C:4]1[C:5]([C:19]2[S:23][C:22]3[CH:24]=[CH:25][CH:26]=[C:27]([C:28]([NH2:30])=[O:29])[C:21]=3[CH:20]=2)=[N:6][C:7]([NH:10][CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:1])[CH2:15][CH2:14]2)=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 688566752-[5-Chloro-2-(2-piperidin-4-ylethylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid amide

Product 1

HCID 688560452-{5-Chloro-2-[2-(1-methylpiperidin-4-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid amide di-hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Aqueous formaldehyde (37.4% or 13.5 M, 0.134 mL, 1.80 mmol) is added to a stirred solution of 2-[5-chloro-2-(2-piperidin-4-ylethylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid amide (150 mg, 0.361 mmol) in CH3OH (15 mL) and dichloromethane (15 mL) at room temperature to form a light suspension. The mixture is allowed to stir for 90 minutes. The mixture is cooled to 0° C. before it is treated with powdered sodium borohydride (68.1 mg, 1.80 mmol). The mixture is stirred at 0° C. for 1 hour, then allowed to slowly warm up to room temperature to form a clear solution. After concentration, the crude product is subject to chromatographic purification on silica gel, eluting with 2 M NH3/CH3OH in dichloromethane 4-12%, to give the desired methylated product as a yellowish solid. The free base is dissolved in CH3OH (20 mL) and dichloromethane (20 mL) then treated with 12 N HCl (0.30 mL) to form a yellow solution. After concentration and vacuum drying at 60° C., the title compound is obtained as a yellow solid (174 mg, 95% yield). ES+(m/z) 430 (35Cl) and 432 (37Cl) [M(free base)+H].

Workup

  1. customto form a light suspension
  2. stirringThe mixture is stirred at 0° C. for 1 hour
  3. temperatureto slowly warm up to room temperature
  4. customto form a clear solution
  5. concentrationAfter concentration
  6. customthe crude product is subject to chromatographic purification on silica gel
  7. washeluting with 2 M NH3/CH3OH in dichloromethane 4-12%
  8. customto give the
  9. customto form a yellow solution
  10. concentrationAfter concentration and vacuum
  11. customdrying at 60° C.

Sources & evidence

ORD record
ord-64208bb050fd40fdb1787fe408926e7f
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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