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US 11,220,507 B2Granted
Process for the preparation of rucaparib and novel synthesis intermediates
AssigneeAdvitech Advisory and Technologies SA
InventorsBrent Christopher Beck, Joe B. Perales, Jason D. Speake, Ilaria Ferrando
Life of this patent
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Abstract
The present invention relates to a process for the preparation of rucaparib; the invention also refers to novel intermediates of synthesis as well as their use in the preparation of i.a. rucaparib.
Claims13
A process for the preparation of of rucaparib of formula (I),
- or a salt thereof, which comprises:
- a) reacting a compound of formula (II)
- wherein
- R1 is selected from hydrogen a halogen atom, a cyano group, a sulfonyl group, an —O— sulfonyl group;
- and
- R2 is selected from hydrogen, an alkyl group, an aryl group or an aryl-alkylgroup;
- or a salt thereof,
- with a compound of formula (III)
- wherein R3 is a protecting group;
- R4 is hydrogen or a protecting group;
- and
- R5 is a protecting group;
- or R4 and R5, together with the nitrogen atom to which they are bound, form a cyclic protecting group;
- to obtain a compound of formula (IV)
- b) converting compound (IV) into the corresponding lactam of formula (V)
- c) when R1 is other than a hydrogen atom, removing R1 from the lactam of formula (V) to obtain rucaparib of formula (I);
- d) optionally, transforming rucaparib in a salt thereof.
14 more elements
A compound selected from a compound of formula (II)
- wherein R1 is selected from hydrogen a halogen atom, a cyano group, a sulfonyl group, an —O-sulfonyl group;
- and
- R2 is selected from hydrogen, an alkyl group, an aryl group or an aryl-alkylgroup;
- or a salt thereof;
- a compound of formula (III)
- wherein R3 is a protecting group;
- R4 is hydrogen or a protecting group;
- and
- R5 is a protecting group;
- or R4 and R5, together with the nitrogen atom to which they are bound, form a cyclic protecting group;
- a compound of formula (IV)
- a compound of formula (V)
- a compound of formula (VI)
- a compound of formula (VIII)
- and
- a compound of formula (IX)
- provided that R1 is not a hydrogen atom in compound of formula (V), as well as their salts.
14 more elements
Crystalline form of rucaparib showing the XRPD:
- Angle
- D Value
- Net Intensity
- Gross Intensity
- Rel Intensity
- 6.907
- 12.78733
- 2405
- 2994
- 21.8%
- 7.954
- 11.10643
- 2488
- 2946
- 22.5%
- 11.178
- 7.90909
- 801
- 1176
- 7.3%
- 11.703
- 7.55534
- 2437
- 2813
- 22.1%
- 12.205
- 7.24602
- 461
- 838
- 4.2%
- 12.405
- 7.12970
- 2962
- 3339
- 26.8%
- 13.804
- 6.41007
- 384
- 764
- 3.5%
- 14.308
- 6.18523
- 413
- 793
- 3.7%
- 14.908
- 5.93775
- 2367
- 2748
- 21.4%
- 15.206
- 5.82210
- 993
- 1375
- 9.0%
- 15.805
- 5.60252
- 2088
- 2471
- 18.9%
- 15.952
- 5.55125
- 1662
- 2045
- 15.1%
- 16.612
- 5.33239
- 1091
- 1474
- 9.9%
- 16.707
- 5.30219
- 1187
- 1571
- 10.8%
- 16.957
- 5.22451
- 711
- 1095
- 6.4%
- 17.160
- 5.16330
- 528
- 912
- 4.8%
- 17.505
- 5.06216
- 274
- 659
- 2.5%
- 18.156
- 4.88217
- 1297
- 1682
- 11.7%
- 18.808
- 4.71427
- 651
- 1037
- 5.9%
- 19.759
- 4.48962
- 1236
- 1622
- 11.2%
- 20.461
- 4.33697
- 376
- 762
- 3.4%
- 21.112
- 4.20486
- 376
- 762
- 3.4%
- 21.961
- 4.04410
- 1340
- 1726
- 12.1%
- 22.461
- 3.95521
- 1414
- 1800
- 12.8%
- 22.809
- 3.89566
- 2464
- 2850
- 22.3%
- 23.602
- 3.76658
- 771
- 1156
- 7.0%
- 23.961
- 3.71094
- 1905
- 2290
- 17.3%
- 24.510
- 3.62892
- 11038
- 11423
- 100.0%
- 25.218
- 3.52875
- 582
- 966
- 5.3%
- 25.559
- 3.48243
- 2961
- 3344
- 26.8%
- 26.013
- 3.42256
- 1032
- 1415
- 9.4%
- 26.562
- 3.35309
- 872
- 1255
- 7.9%
- 27.012
- 3.29826
- 1225
- 1606
- 11.1%
- 27.761
- 3.21095
- 660
- 1040
- 6.0%
- 28.213
- 3.16058
- 826
- 1206
- 7.5%
- 28.664
- 3.11182
- 576
- 955
- 5.2%
- 29.816
- 2.99418
- 566
- 943
- 5.1 %
- 30.564
- 2.92260
- 447
- 822
- 4.1 %
- 32.260
- 2.77270
- 1308
- 1679
- 11.9%
- 33.865
- 2.64482
- 440
- 806
- 4.0%
- 35.017
- 2.56043
- 441
- 804
- 4.0%
- 39.176
- 2.29766
- 271
- 637
- 2.5%.
212 more elements
Dependencies are inferred from the claim text.