Hydrochloric Acid → HCID 69813290, compound

HRID 529116Notes

Reaction equation

HRID 529116 reaction equation
[N+](C1C=CC(C([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[C:33]5[C:28](=[C:29]([CH2:35][NH:36][CH:37]([CH3:39])[CH3:38])[C:30]([Cl:34])=[CH:31][CH:32]=5)[C:22]5([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]5)[CH2:21]4)[C:14]=3[C@H:13]([CH3:40])[CH2:12]2)=O)=CC=1)([O-])=O.O[Li].O.[ClH:46]>C1COCC1.C(Cl)Cl.CCOCC>[ClH:34].[ClH:46].[ClH:34].[Cl:34][C:30]1[C:29]([CH2:35][NH:36][CH:37]([CH3:39])[CH3:38])=[C:28]2[C:22]3([CH2:23][CH2:24][NH:25][CH2:26][CH2:27]3)[CH2:21][N:20]([C:19]3[C:14]4[C@H:13]([CH3:40])[CH2:12][C@@H:11]([OH:10])[C:15]=4[N:16]=[CH:17][N:18]=3)[C:33]2=[CH:32][CH:31]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 69812443HCID 69812443, compound

Product 1

HCID 69813290HCID 69813290, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (5R,7R)-4-(5-chloro-4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (6 mg, 0.01 mmol) in THF (0.2 mL) was cooled to 0° C. and treated with 1N LiOH—H2O (0.020 mL, 0.020 mmol). The reaction was stirred at room temperature overnight. The reaction was partitioned between DCM and saturated aqueous NaHCO3 solution. The aqueous layer was extracted with DCM. The combined organic layers were washed with brine, dried, and concentrated. The crude residue was purified by column chromatography (10% 7N ammonia in MeOH/DCM) to yield the free base, which was taken up in DCM and acidified with 2N HCl in Et2O. The solvents were removed in vacuo. (5R,7R)-4-(5-chloro-4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride (4 mg, 71%) was obtained as a solid. LCMS (APCI+) m/z 442, 444 [M+H]+; Rt=1.90 min.

Workup

  1. customThe reaction was partitioned between DCM and saturated aqueous NaHCO3 solution
  2. extractionThe aqueous layer was extracted with DCM
  3. washThe combined organic layers were washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe crude residue was purified by column chromatography (10% 7N ammonia in MeOH/DCM)
  7. customto yield the free base, which
  8. customThe solvents were removed in vacuo

Sources & evidence

ORD record
ord-38e5c4fcad9e47b79c0fd92b00b6ce19
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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