4-[4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)-carbonyl]aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate → N2-{4-[4-amino-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

HRID 897865Notes

Reaction equation

HRID 897865 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:32]3[CH:37]=[CH:36][N+:35]([O-])=[CH:34][CH:33]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12.O.[PH2]([O-])=O.[Na+].[PH2]([O-])=O.[Na+]>[Pd].C(O)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:32]3[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12

Participants

6

Reactant 3

HCID 692045684-[4-amino-3-(3-methoxy-4-[(1-methyl-1H-2-indolyl)-carbonyl]aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolateHCID 178418950HCID 178418950, compoundHCID 178527019HCID 178527019, compound

Product 1

HCID 22346897N2-{4-[4-amino-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamideYield 10.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 176Acetic AcidSolvent

Procedure

A suspension of 4-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate (0.200 g, 0.00039 mol) and 10% palladium on carbon (0.042 g, 0.00004 mol) in acetic acid (3 mL) was reacted with sodium hypophosphite monohydrate (0.063 g, 0.00059 mol) at 60° C. for 2 hours. Additional 10% palladium on carbon (0.042 g, 0.00004 mol) and sodium hypophosphite (0.045 g, 0.00042 mol ) was added and the mixture was stirred for 24 hours. The solvent was removed in vacuo and the residue was slurried in methanol for 4 hours. The mixture was filtered through Celite® 521, washing with methanol. The solvent was removed in vacuo and the residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 A, 25 cm; 50% isocratic for five minutes, then 50%-100% acetonitrile-0.1M ammonium acetate over 25 min, 21 ml/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give N2-{4-[4-amino-1-(4-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide (0.020 g, 0.00004 mol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.48 (s, 1H) 8.72 (d, 2H), 8.47 (s, 1H), 8.42 (d, 2H), 8.20 (d, 1H), 7.72 (d, 1H), 7.60 (d, 1H), 7.48 (s, 1H), 7.42 (d, 1H), 7.36 (s, 1H) 7.34 (t, 1H), 7.16 (t, 1H), 4.05 (s, 3H), 3.99 (s, 1H); RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 19.50 min.;

Workup

  1. customThe solvent was removed in vacuo
  2. waitthe residue was slurried in methanol for 4 hours
  3. filtrationThe mixture was filtered through Celite® 521
  4. washwashing with methanol
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by preparative RP-HPLC (Rainin C18, 8 mm, 300 A, 25 cm
  7. wait50% isocratic for five minutes
  8. wait50%-100% acetonitrile-0.1M ammonium acetate over 25 min
  9. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-575b1e9f5c4a4746a796adc9cb948385
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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