Diisopropylethylamine → HCID 178476644, compound

HRID 897981Notes

Reaction equation

HRID 897981 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].[OH:33]N1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C([N:58]([CH2:62][CH3:63])[CH:59]([CH3:61])[CH3:60])(C)C>CN(C)C=O>[C:3]([OH:31])(=[O:33])[CH3:4].[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:61]([C@H:59]4[CH2:60][CH2:63][CH2:62][NH:58]4)=[O:33])=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178488198HCID 178488198, compound

Product 1

HCID 178476644HCID 178476644, compoundYield 69.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of trans 3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.200 g, 0.00046 mol) in N,N-dimethylformamide (10 mL) was reacted with 1-hydroxy-7-azabenzotriazole (0.068 g, 0.00050 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.132 g, 0.00069 mol), D-Boc-proline (0.108 g, 0.00050 mol) and N,N-diisopropylethylamine (0.184 g, 0.00142 mol) at ambient temperature for 24 hours. The solvent was removed in vacuo and the residue was partitioned between dichloromethane (10 mL) and a 5% aqueous citric acid solution (20 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×10 mL). The combined organic phases were washed with saturated aqueous sodium bicarbonate (15 mL) and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was stirred in 20% trifluoroacetic acid in dichloromethane for 6 hours at ambient temperature. The solvent was removed in vacuo and the residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 A, 25 cm; 5% isocratic for five minutes, then 5%-40% acetonitrile-0.1M ammonium acetate over 20 min, 21 ml/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give trans N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(2R)tetrahydro-1H-2-pyrrolecarboxamide acetate (0.096 g, 0.00016 mol) as a white solid.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between dichloromethane (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×10 mL)
  5. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate (15 mL)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe solvent was removed in vacuo
  9. customthe residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 A, 25 cm
  10. wait5% isocratic for five minutes
  11. wait5%-40% acetonitrile-0.1M ammonium acetate over 20 min
  12. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-cb73f454dc8e438fa11ffef15e875b6f
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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