Hydrochloric Acid → Ipatasertib Hydrochloride

HRID 628814Notes

Reaction equation

HRID 628814 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[C:30]4[C@H:37]([CH3:38])[CH2:36][C@@H:35]([OH:39])[C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:25][CH2:24]2)=[O:22])[CH2:9][N:10]([CH:18]([CH3:20])[CH3:19])C(=O)OC(C)(C)C)=[CH:4][CH:3]=1.Cl.N1CCNCC1>C(O)CC>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH2:9][NH:10][CH:18]([CH3:20])[CH3:19])[C:21]([N:23]2[CH2:24][CH2:25][N:26]([C:29]3[C:30]4[C@H:37]([CH3:38])[CH2:36][C@@H:35]([OH:39])[C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:27][CH2:28]2)=[O:22])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4837Piperazine2×HCID 66618379tert-butyl ((S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl)(isopropyl)carbamate

Product 1

HCID 72188570Ipatasertib Hydrochloride

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent3×

Procedure

To a solution of tert-butyl ((S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl)(isopropyl)carbamate (50 g) in 1-propanol (128 g) was added HCl in 1-propanol (45.2 g, 5.5N). The solution was heated until complete deprotection. The solution was cooled to room temperature and then a solution of piperazine (7.3 g) in 1-propanol (36.5 g) was added dropwise. The resulting solid piperazine.HCl was filtered off and the filtrate was carbon treated, concentrated and solvent-switched to ethyl acetate. The resulting solid (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one monohydrochloride was filtered and washed with ethyl acetate and dried under vacuum (Yield 22.9 g, 99.8% purity by LC).

Workup

  1. temperatureThe solution was heated until complete deprotection
  2. filtrationHCl was filtered off
  3. additiontreated
  4. concentrationconcentrated
  5. filtrationThe resulting solid (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one monohydrochloride was filtered
  6. washwashed with ethyl acetate
  7. customdried under vacuum (Yield 22.9 g, 99.8% purity by LC)

Sources & evidence

ORD record
ord-a602b63960c0496f832aa7832adffb33
Source dataset
uspto-grants-2016_04
Patent number
US09315471B2

Reaction notes

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