Methanesulfonyl chloride → 2-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate

HRID 2056016Notes

Reaction equation

HRID 2056016 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:32][CH2:33][OH:34])[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.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>N1C=CC=CC=1>[CH3:35][S:36]([O:34][CH2:33][CH2:32][N:8]1[C:4]2=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]2[C:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[N:21]([CH3:29])[C:22]4[C:27]([CH:28]=3)=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=2)=[N:9]1)(=[O:38])=[O:37]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 22346971N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

Product 1

HCID 223468312-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonateYield 66.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. mixture of N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide (0.343 g, 0.750 mmol) and pyridine (7.5 mL) was added methanesulfonyl chloride (0.14 mL, 1.8 mmol) dropwise over 30 sec. The reaction mixture was stirred at 0° C. for 2 h then ice water (10 mL) was added. The precipitate was collected by filtration and dried in vacuo to afford 2-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate as a beige solid (0.268 g, 0.500 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.30 (1H, s), 8.13 (1H, d, J=8.0 Hz), 7.70 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=8.4 Hz), 7.31-7.38 (4H, m), 7.15 (1H, t, J=7.6 Hz), 4.70 (3H, s), 4.04 (3H, s), 3.96 (3H, s), 3.37 (2H, obscured by water peak), and 3.12 (2H, s); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 11.22 min. MS: M+ 536.2.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. customdried in vacuo

Sources & evidence

ORD record
ord-153d092c5fa24f9099604fbd6f86e000
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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