Sodium Carbonate → tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamate

HRID 82389Notes

Reaction equation

HRID 82389 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[CH3:27][C@H:28]1[C:36]2[C:35]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[N:34][CH:33]=[N:32][C:31]=2[CH2:30][CH2:29]1.[C:43]([O:47][C:48]([NH:50][CH2:51][C@H:52]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=1)[C:53](O)=[O:54])=[O:49])([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CC(=O)OCC>[Cl:62][C:59]1[CH:60]=[CH:61][C:56]([C@H:52]([C:53]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[C:36]4[C@H:28]([CH3:27])[CH2:29][CH2:30][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38][CH2:39]2)=[O:54])[CH2:51][NH:50][C:48](=[O:49])[O:47][C:43]([CH3:46])([CH3:44])[CH3:45])=[CH:57][CH:58]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25178695(R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochlorideHCID 29947824HCID 29947824, compound

Product 1

HCID 86618948tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamateYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

HBTU (0.033 g, 0.086 mmol) was added to a solution of (R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (0.025 g, 0.086 mmol), (S)-3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoic acid (0.026 g, 0.086 mmol), and DIEA (0.045 mL, 0.26 mmol) in DCM (1.2 mL). The reaction mixture was stirred at room temperature for 90 minutes. 2M Na2CO3 was added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on Biotage 12S (ca. 100 mL; 4:1 DCM:EA flushed to elute DIEA, then 1:9 DCM:EA eluted product) to give tert-butyl(S)-2-(4-chlorophenyl)-3-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropylcarbamate (0.043 g, 100% yield) as a yellow residue. LC/MS (APCI+) m/z 500.1 [M+H]+; Rf: 2.68.

Workup

  1. extractionthe mixture was extracted with DCM
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custom4:1 DCM:EA flushed
  6. washto elute DIEA

Sources & evidence

ORD record
ord-bc14431bb37b4c52b54c909a7451f065
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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