Hydrochloric Acid → (S)-2-(4-chlorophenyl)-3-(cyclopropylmethylamino)-1-(4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one

HRID 2200311Notes

Reaction equation

HRID 2200311 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][C@H:36]([OH:40])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH2:26][CH2:25]2)=[O:23])[CH2:9][N:10]([CH2:18][CH:19]2[CH2:21][CH2:20]2)C(=O)OC(C)(C)C)=[CH:4][CH:3]=1.Cl>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH2:9][NH:10][CH2:18][CH:19]2[CH2:21][CH2:20]2)[C:22]([N:24]2[CH2:25][CH2:26][N:27]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][C@H:36]([OH:40])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH2:28][CH2:29]2)=[O:23])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66617928HCID 66617928, compound

Product 1

HCID 59670880(S)-2-(4-chlorophenyl)-3-(cyclopropylmethylamino)-1-(4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(cyclopropylmethyl)carbamate (0.0674 g, 0.1182 mmol) was dissolved in dioxane (0.5 mL) and treated with HCl in dioxane (0.7389 ml, 2.956 mmol) (4M). The reaction was stirred at ambient temperature for 48 hours. The reaction mixture was concentrated in vacuo. The residue was redissolved in MeOH and re-concentrated three times. This residue was resuspended in MeOH (0.2+0.1 mL) and added dropwise to a stirred flask of Et2O (10 mL). After stirring for 30 minutes, the solids were filtered, washed with Et2O, and dried under a blanket of nitrogen to give (S)-2-(4-chlorophenyl)-3-(cyclopropylmethylamino)-1-(4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one as a white solid (60.2 mg, 94%.) LCMS (APCI+) [M+H]+ 470.2.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was redissolved in MeOH
  3. concentrationre-concentrated three times
  4. additionadded dropwise to a stirred flask of Et2O (10 mL)
  5. stirringAfter stirring for 30 minutes
  6. filtrationthe solids were filtered
  7. washwashed with Et2O
  8. customdried under a blanket of nitrogen

Sources & evidence

ORD record
ord-8226fcbe6fd74c328a931cbb1e9c8415
Source dataset
uspto-grants-2016_06
Patent number
US09359340B2

Reaction notes

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