An improved process for the preparation of ibrutinib
AssigneeNatco Pharma Limited
InventorsPulla Reddy MUDDASANI, Shankar Reddy BUDIDETI, Veerababu MADALAPU, Anitha GATTU, Bala Ankireddy KONDA, Venkaiah Chowdary NANNAPANENI
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Abstract
The present invention relates to an improved process for the preparation of Ibrutinib with high purity and high yields. The present process is cost effective and feasible in large scale production also. The present process avoids the mitsunobu reagent conditions also. The present Invention also relates to a process for the preparation of Crystalline form A and Crystalline form C of Ibrutinib.
Claims10
A process for the preparation of Ibrutinib comprising the steps of:
- a) reacting (S)-1-boc-3-hydroxy piperidine with methane sulfonyl chloride to get (S)-1-boc-3-methylsulfonyloxy piperidine,
- b) treating (S)-1-boc-3-methylsulfonyloxy piperidine with 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine in presence of inorganic base or mixture of inorganic bases to get (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride,
- c) reacting (R)-3 -(4-phenoxyphenyl)-1-(piperidin-3 -yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride with base followed by acryloyl chloride to obtain ibrutinib,
- d) optionally purifying the ibrutinib.
A process for the preparation of Ibrutinib Crystalline form A comprising the steps of:
- a) reacting (S)-1-boc-3-hydroxy piperidine with methane sulfonyl chloride to get (S)-1-boc-3-methylsulfonyloxy piperidine,
- b) treating (S)-1-boc-3-methylsulfonyloxy piperidine with 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine in presence of inorganic base or mixture of inorganic bases to get (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride,
- c) reacting (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride with base followed by acryloyl chloride to obtain ibrutinib,
- d) optionally purifying the ibrutinib,
- e) dissolving ibrutinib in polar aprotic solvent and
- f) isolating Crystalline form A of ibrutinib.
A process for the preparation of Ibrutinib Crystalline form C comprising the steps of:
- a) reacting (S)-1-boc-3-hydroxy piperidine with methane sulfonyl chloride to get (S)-1-boc-3-methylsulfonyloxy piperidine,
- b) treating (S)- 1-boc-3-methyl sulfonyloxy piperidine with 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine in presence of inorganic base or mixture of inorganic bases to get (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride,
- c) reacting (R)-3 -(4-phenoxyphenyl)-1-(piperidin-3-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine hydrochloride with base followed by acryloyl chloride to obtain ibrutinib,
- d) optionally purifying the ibrutinib,
- e) dissolving ibrutinib in polar protic solvent and
- f) isolating Crystalline form C of ibrutinib.
A process for the preparation of Crystalline form A of Ibrutinib comprising the steps of:
- a) dissolving ibrutinib in polar aprotic solvent and
- b) isolating Crystalline form A of ibrutinib.
A process for the preparation of Crystalline form C of Ibrutinib comprising the steps of:
- a) dissolving ibrutinib in polar protic solvent and
- b) isolating Crystalline form C of ibrutinib.
A process for the purification of ibrutinib comprising the steps of:
- a) dissolving ibrutinib in methylene chloride and toluene, and
- b) isolating pure ibrutinib.
Dependencies are inferred from the claim text.