Ethanolamine → Rucaparib

HRID 2253293Notes

Reaction equation

HRID 2253293 reaction equation
CO[C:3](=O)[N:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[NH:14][C:15]3[CH:16]=[C:17]([F:27])[CH:18]=[C:19]4[C:25](=[O:26])[NH:24][CH2:23][CH2:22][C:21]=2[C:20]=34)=[CH:9][CH:8]=1)C.C(CN)O.[OH-].[Na+]>Br.C(O)(=O)C>[F:27][C:17]1[CH:18]=[C:19]2[C:25](=[O:26])[NH:24][CH2:23][CH2:22][C:21]3=[C:13]([C:10]4[CH:9]=[CH:8][C:7]([CH2:6][NH:4][CH3:3])=[CH:12][CH:11]=4)[NH:14][C:15]([CH:16]=1)=[C:20]23

Participants

6

Reactant 3

HCID 700EthanolamineHCID 14798Sodium Hydroxide2×HCID 58615943methyl (4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)carbamate

Product 1

HCID 9931954RucaparibYield 88%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

Lactam 14 (14.42 g, 0.038 mol) was dissolved in hydrobromic acid in acetic acid (30%-32%, 140 ml). The reaction solution was stirred for 46 hours at room temperature in a 500 ml flask that was connected to an ethanolamine scrubber system. HPLC analysis indicated the completion of the reaction. Ice (30 g) was added to the reaction solution followed by addition of aqueous NaOH (327 ml, 10 M, 3.27 mol) while the temperature was maintained between 25° C. and 35° C. When addition of NaOH was complete, the pH was 10. The resulting solid was collected by filtration, washed with water (2×50 ml). The filter cake was then suspended in water (125 ml) and stirred for 2 hours. The solid was collected by filtration, washed with water (2×25 ml) and dried to afford 10.76 g of product (88% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.577 (s, 3H), 3.053 (m, 2H), 3.406 (m, 2H), 4.159 (s, 2H), 7.36 (dd, 1H, J=2.4 Hz and J=9.3 Hz), 7.44 (dd, 1H, J=2.4 Hz and J=11.1 Hz), 7.63 (d, 2H, J=8.1 Hz), 7.70 (d, 2H, J=8.1 Hz), 8.265 (t, 1H, J=5.7 Hz), 11.77 (s, 1H). Exact mass calculated for C19H19FN3O: 324.1512. Found: 324.1497.

Workup

  1. customthe completion of the reaction
  2. temperaturewas maintained between 25° C. and 35° C
  3. filtrationThe resulting solid was collected by filtration
  4. washwashed with water (2×50 ml)
  5. stirringstirred for 2 hours
  6. filtrationThe solid was collected by filtration
  7. washwashed with water (2×25 ml)
  8. customdried

Sources & evidence

ORD record
ord-83d353cacaec49a88773f96fd7315b1e
Source dataset
uspto-grants-2008_01
Patent number
US07323562B2

Reaction notes

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