Hydrochloric Acid → HCID 67339075, compound

HRID 82414Notes

Reaction equation

HRID 82414 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]([F: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.[ClH:41]>O1CCOCC1>[ClH:1].[ClH:41].[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]([F: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 67338647HCID 67338647, compound

Product 1

HCID 67339075HCID 67339075, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

tert-butyl(S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(cyclopropylmethyl)carbamate (0.955 g, 1.669 mmol) was dissolved in dioxane (20 mL). The solution was treated with HCl in dioxane (10.43 mL, 41.73 mmol; 4M), and the mixture was stirred at ambient temperature for 16 hours. HPLC showed no SM remaining, so the reaction mixture was concentrated in vacuo, re-dissolved in MeOH and re-concentrated (3×). The residue was re-dissolved in MeOH (about 4.5 mL+2 mL wash) and added dropwise to stirred ether (about 190 mL). The suspension was stirred for 30 minutes then filtered and dried under nitrogen blanket to give (S)-2-(4-chlorophenyl)-3-(cyclopropylmethylamino)-1-(4-((5R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)propan-1-one dihydrochloride (797 mg, 88%) as a solid. LC/MS (APCI+, FIA) m/z 472.2/474.2 [M+H]+

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionre-dissolved in MeOH
  3. concentrationre-concentrated (3×)
  4. dissolutionThe residue was re-dissolved in MeOH (about 4.5 mL+2 mL wash)
  5. additionadded dropwise
  6. stirringto stirred ether (about 190 mL)
  7. stirringThe suspension was stirred for 30 minutes
  8. filtrationthen filtered
  9. customdried under nitrogen blanket

Sources & evidence

ORD record
ord-79045fa50f234136829b897455385802
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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