Hydrochloric Acid → HCID 68736829, compound

HRID 529081Notes

Reaction equation

HRID 529081 reaction equation
C(OC([NH:8][CH2:9][CH:10]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[O:11][C:12]1[CH:13]=[C:14]2[C:20]3([CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[CH2:19][N:18]([C:33]3[C:34]4[C@H:41]([CH3:42])[CH2:40][CH2:39][C:35]=4[N:36]=[CH:37][N:38]=3)[C:15]2=[CH:16][CH:17]=1)=O)(C)(C)C.[ClH:49]>C(Cl)Cl.O1CCOCC1.CCOCC>[ClH:49].[ClH:49].[ClH:49].[CH3:42][C@H:41]1[C:34]2[C:33]([N:18]3[C:15]4[C:14](=[CH:13][C:12]([O:11][CH:10]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=5)[CH2:9][NH2:8])=[CH:17][CH:16]=4)[C:20]4([CH2:21][CH2:22][NH:23][CH2:24][CH2:25]4)[CH2:19]3)=[N:38][CH:37]=[N:36][C:35]=2[CH2:39][CH2:40]1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 71268454HCID 71268454, compound

Product 1

HCID 68736829HCID 68736829, compoundYield 5%

Reagents, catalysts & solvents 3

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

Procedure

A solution of tert-butyl 5-(2-(tert-butoxycarbonylamino)-1-phenylethoxy)-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.235 g, 0.358 mmol) in DCM (4 mL) was treated with 4N HCl in dioxane (1 mL). The reaction was stirred at about room temperature overnight. The solvents were removed and the crude residue was partitioned between DCM and 1N HCl. The aqueous phase was extracted with DCM (×3), and then basified with 1N NaOH. The free base was extracted with DCM. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase column chromatography (0-60% ACN/H2O) to give the free base, which was taken up in DCM and acidified with 2N HCl in ether. Removal of the solvents under reduced pressure afforded 2-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yloxy)-2-phenylethanamine trihydrochloride (0.008 g, 5%). LCMS (APCI+) m/z 456.2 [M+H]+; Rt=2.49 min.

Workup

  1. customThe solvents were removed
  2. customthe crude residue was partitioned between DCM and 1N HCl
  3. extractionThe aqueous phase was extracted with DCM (×3)
  4. extractionThe free base was extracted with DCM
  5. washThe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by reverse phase column chromatography (0-60% ACN/H2O)
  10. customto give the free base, which
  11. customRemoval of the solvents under reduced pressure

Sources & evidence

ORD record
ord-23ed2dae64d842619c3ced5324081f8b
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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