Sodium Iodide → N2-(4-{4-amino-1-[1-(2-fluoroethyl)-4-piperidyl]-1H-pyrazolo [3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

HRID 2056188Notes

Reaction equation

HRID 2056188 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]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.Br[CH2:39][CH2:40][F:41].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:37][CH2:36][N:35]([CH2:39][CH2:40][F:41])[CH2:34][CH2:33]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

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 129822-Fluoroethyl bromideHCID 20817350HCID 20817350, compound

Product 1

HCID 22346950N2-(4-{4-amino-1-[1-(2-fluoroethyl)-4-piperidyl]-1H-pyrazolo [3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamideYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

N2-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-methyl-1H-2-indolecarboxamide (250 mg, 0.503 mmol), 1-bromo-2-fluoroethane (47 ul, 0.629 mmol), Potassium carbonate (87 mg, 0.629 mmol) and Sodium iodide (10 mg, 0.066 mmol) were mixed in DMF (3 mL). The reaction mixture was heated at 80° C. overnight. The crude reaction mixture was purified by reverse phase preparative HPLC using acetonitrile/water (50 mM ammonium acetate buffer) as mobile phase to give N2-(4-{4-amino-1-[1-(2-fluoroethyl)-4-piperidyl]-1H-pyrazolo [3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (221 mg, 81%). 1H NMR (DMSO-d6) δ 1.91 (m, 2H), 2.26 (m, 4H), 2.66 (m, 1H), 2.73 (m, 1H), 3.05 (m, 2H), 3.97 (s, 3H), 4.04 (s, 3H), 4.61 (m, 1H), 4.61 (m, 1H), 4.64 (m, 1H), 7.15 (m, 1H), 7.33 (m, 4H), 7.58 (d, J=8.46 Hz, 1H), 7.70 (d, J=7.95 Hz, 1H), 8.11 (d, J=8.14 Hz, 1H), 8.25 (s, 1H), 9.44 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 0.8 mL/min.): RT=2.17 min. MH+=543.3.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-32db7ee2662849cb96ff15ec8615f826
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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