Hydrochloric Acid → HCID 68735430, compound

HRID 529119Notes

Reaction equation

HRID 529119 reaction equation
[ClH:1].C(OC([N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]2[N:20]([C:35]3[C:36]4[C@H:43]([CH3:44])[CH2:42][C@H:41]([F:45])[C:37]=4[N:38]=[CH:39][N:40]=3)[CH2:21][C:22]3([CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[C:15]=12)[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C>O1CCOCC1.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[ClH:1].[F:45][C@@H:41]1[C:37]2[N:38]=[CH:39][N:40]=[C:35]([N:20]3[C:16]4[C:15](=[C:14]([CH2:13][NH:9][CH:10]([CH3:12])[CH3:11])[CH:19]=[CH:18][CH:17]=4)[C:22]4([CH2:23][CH2:24][NH:25][CH2:26][CH2:27]4)[CH2:21]3)[C:36]=2[C@H:43]([CH3:44])[CH2:42]1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 69812441HCID 69812441, compound

Product 1

HCID 68735430HCID 68735430, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

4N HCl in dioxane (0.1 mL) was added to a solution of tert-butyl 4-((tert-butoxycarbonyl(isopropyl)amino)methyl)-1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (12 mg, 0.020 mmol) in DCM (0.3 mL). The reaction mixture was stirred at room temperature overnight. The solvents were evaporated. The crude residue was taken up in MeOH and basified with 7N ammonia in MeOH. After evaporation of the solvent, the residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM) to yield the free base, which was taken up in DCM and acidified with 2N HCl in Et2O. Removal of the solvents afforded N-((1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine trihydrochloride (9 mg, 88%) as a solid. LCMS (APCI+) m/z 410 [M+H]+; Rt=1.55 min.

Workup

  1. customThe solvents were evaporated
  2. customAfter evaporation of the solvent
  3. customthe residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM)
  4. customto yield the free base, which
  5. customRemoval of the solvents

Sources & evidence

ORD record
ord-1dc13cf13b244e28ab109a1ea4597d48
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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