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 2056063Notes

Reaction equation

HRID 2056063 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, 300A, 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-973be3767d694fcd828d7ba44fedc261
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

Loading…