Hydrochloric Acid → HCID 86679242, compound

HRID 529092Notes

Reaction equation

HRID 529092 reaction equation
[ClH:1].Cl.[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][C@@H:24]([OH:28])[C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1.[CH3:29]CN(C(C)C)C(C)C.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].Cl>ClCCCl.C1COCC1.C(Cl)Cl.CCOCC>[ClH:3].[ClH:1].[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][N:15]([CH3:29])[CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][C@@H:24]([OH:28])[C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 69810675HCID 69810675, compound

Product 1

HCID 86679242HCID 86679242, compound

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of (5R,7R)-4-(5-chlorospiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (10 mg, 0.027 mmol) in DCE (0.5 mL) was added DIEA (0.009 mL, 0.05 mmol). The suspension was shaken until dissolved. Formaldehyde (37% w/w in water, 0.022 mL, 0.27 mmol) was added as a solution in THF (0.15 mL). The reaction was allowed to stir at about room temperature for about 15 minutes at which point Na(OAc)3BH was added and the reaction allowed to stir overnight. The reaction mixture was diluted with DCM, washed with saturated aqueous NaHCO3 solution and brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 8:1) 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 (5R,7R)-4-(5-chloro-1′-methylspiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride. LCMS (APCI+) m/z 385, 387 [M+H]+; Rt=2.18 min.

Workup

  1. dissolutionuntil dissolved
  2. additionwas added
  3. stirringto stir overnight
  4. washwashed with saturated aqueous NaHCO3 solution and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (DCM:MeOH, 8:1)
  8. customto give the free base, which
  9. customRemoval of the solvents under reduced pressure

Sources & evidence

ORD record
ord-9602c390b6854971a4944f7d5a16f3de
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

Loading…