Acetone → (5R,7R)-4-(3-(1-(4-chlorophenyl)-2-(isopropylamino)ethyl)benzo[d]isothiazol-6-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride

HRID 340156Notes

Reaction equation

HRID 340156 reaction equation
CCN(C(C)C)[CH:4]([CH3:6])[CH3:5].[ClH:10].Cl.Cl.[NH2:13][CH2:14][CH:15]([C:23]1[C:27]2[CH:28]=[CH:29][C:30]([C:32]3[C:33]4[C@H:40]([CH3:41])[CH2:39][C@@H:38]([OH:42])[C:34]=4[N:35]=[CH:36][N:37]=3)=[CH:31][C:26]=2[S:25][N:24]=1)[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1.CC(C)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].Cl>ClCCCl.C1COCC1.C(Cl)Cl.CCOCC>[ClH:22].[ClH:10].[ClH:22].[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH:15]([C:23]2[C:27]3[CH:28]=[CH:29][C:30]([C:32]4[C:33]5[C@H:40]([CH3:41])[CH2:39][C@@H:38]([OH:42])[C:34]=5[N:35]=[CH:36][N:37]=4)=[CH:31][C:26]=3[S:25][N:24]=2)[CH2:14][NH:13][CH:4]([CH3:6])[CH3:5])=[CH:21][CH:20]=1

Participants

10

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 67436726(5R,7R)-4-(3-(2-amino-1-(4-chlorophenyl)ethyl)benzo[d]isothiazol-6-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride

Product 1

HCID 67439441(5R,7R)-4-(3-(1-(4-chlorophenyl)-2-(isopropylamino)ethyl)benzo[d]isothiazol-6-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride

Reagents, catalysts & solvents 4

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

Procedure

DIEA (0.035 mL, 0.20 mmol) was added to a stirred suspension of (5R,7R)-4-(3-(2-amino-1-(4-chlorophenyl)ethyl)benzo[d]isothiazol-6-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride (22 mg, 0.050 mmol) in DCE (1.5 mL). The suspension was shaken until dissolved. A solution of acetone (0.022 mL, 0.30 mmol) in THF (0.3 mL) was added. The reaction was allowed to stir at room temperature for 15 minutes, at which point Na(OAc)3BH (27 mg, 0.13 mmol) was added. The reaction was allowed to stir at room temperature for 1 hour. The reaction mixture was diluted with DCM, washed with saturated aqueous NaHCO3 solution and brine, dried and concentrated. The resulting residue was purified by column chromatography (DCM:7N ammonia in MeOH, 30:1) 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 gave (5R,7R)-4-(3-(1-(4-chlorophenyl)-2-(isopropylamino)ethyl)benzo[d]isothiazol-6-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol trihydrochloride. LCMS (APCI+) m/z 479, 481 [M+H]+; Rt=2.69 min.

Workup

  1. dissolutionuntil dissolved
  2. additionwas added
  3. stirringto stir at room temperature for 1 hour
  4. washwashed with saturated aqueous NaHCO3 solution and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe resulting residue was purified by column chromatography (DCM:7N ammonia in MeOH, 30:1)
  8. customto give the free base, which
  9. customRemoval of the solvents under reduced pressure

Sources & evidence

ORD record
ord-bb5e3a27314144f9aabe1e7ca553a8e9
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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