Cyclopropylamine → 2-{5-Chloro-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid cyclopropylamide tri-hydrochloride

HRID 1986234Notes

Reaction equation

HRID 1986234 reaction equation
C(N(C(C)C)CC)(C)C.[CH:10]1([NH2:13])[CH2:12][CH2:11]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[ClH:41].Cl.Cl.[Cl:44][C:45]1[C:46]([C:62]2[S:66][C:65]3[CH:67]=[C:68]([C:71](O)=[O:72])[CH:69]=[CH:70][C:64]=3[CH:63]=2)=[N:47][C:48]([NH:51][CH2:52][CH2:53][CH2:54][N:55]2[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]2)=[N:49][CH:50]=1.[Li+].[Cl-]>CN(C=O)C>[ClH:44].[ClH:41].[ClH:44].[CH:10]1([NH:13][C:71]([C:68]2[CH:69]=[CH:70][C:64]3[CH:63]=[C:62]([C:46]4[C:45]([Cl:44])=[CH:50][N:49]=[C:48]([NH:51][CH2:52][CH2:53][CH2:54][N:55]5[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]5)[N:47]=4)[S:66][C:65]=3[CH:67]=2)=[O:72])[CH2:12][CH2:11]1

Participants

7

Reactant 5

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 433294Lithium ChlorideHCID 688561812-{5-Chloro-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid tri-hydrochloride

Product 1

HCID 688559562-{5-Chloro-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid cyclopropylamide tri-hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (0.210 mL, 1.20 mmol), cyclopropylamine (0.090 mL, 1.3 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (205 mg, 0.460 mmol) are added successively to a stirred suspension of 2-{5-chloro-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid tri-hydrochloride. (195 mg, 0.400 mmol) and LiCl (187 mg, 4.40 mmol) in DMF (4 mL) at ambient temperature under nitrogen, the resultant mixture is heated at 50° C. for 20 hours. After cooling to ambient temperature, the solvent is removed and the residue is subject to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, to give the free base of the title compound (97 mg). ES+(m/z) 485 (35Cl) and 487 (37Cl) [M+H]. Using the method of Preparation (E) in 2-{5-chloro-2-[3-(4-methylpiperazin-1-yl)-propylamino]-pyrimidin-4-yl}-benzo[b]thiophene-4-carboxylic acid cyclopropylamide tri-hydrochloride, the free base is converted to the tri-hydrochloride salt as a yellow solid.

Workup

  1. customthe solvent is removed
  2. washeluting with 2 M NH3/MeOH in dichloromethane 0-8%

Sources & evidence

ORD record
ord-36ad55c9870a4ebfa55fd50770b76bfc
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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