Diisopropylethylamine → (R)-tert-butyl 4-(4-chlorophenyl)-2-methyl-5-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-5-oxopentan-2-ylcarbamate

HRID 82384Notes

Reaction equation

HRID 82384 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][C:51]([CH3:65])([CH3:64])[CH2:52][CH:53]([C:57]1[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=1)[C:54](O)=[O:55])=[O:49])([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].CC(=O)OCC>[Cl:63][C:60]1[CH:59]=[CH:58][C:57]([C@H:53]([C:54]([N:40]2[CH2:41][CH2:42][N:37]([C:35]3[C:36]4[CH:28]([CH3:27])[CH2:29][CH2:30][C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:38][CH2:39]2)=[O:55])[CH2:52][C:51]([NH:50][C:48](=[O:49])[O:47][C:43]([CH3:45])([CH3:44])[CH3:46])([CH3:65])[CH3:64])=[CH:62][CH:61]=1

Participants

8

Reactant 4

HCID 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 666178284-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)-4-methylpentanoic acid

Product 1

HCID 67341311(R)-tert-butyl 4-(4-chlorophenyl)-2-methyl-5-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-5-oxopentan-2-ylcarbamateYield 95%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

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), 4-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)-4-methylpentanoic acid (0.029 g, 0.086 mmol), and DIEA (0.045 mL, 0.26 mmol) in DCM (1.2 mL). The reaction was shaken overnight (16 hours), after which it was diluted with 2M Na2CO3 and extracted with DCM. The extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on Biotage 12S (ca. 100 mL 3:1 DCM:EA flushed to elute DIEA, then 1:3 DCM:EA eluted prod) to give (R)-tert-butyl 4-(4-chlorophenyl)-2-methyl-5-(4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-5-oxopentan-2-ylcarbamate (0.044 g, 95% yield) as a residue. LCMS (APCI+) [M+H]+ 542.2; Rt: 2.94 min.

Workup

  1. extractionextracted with DCM
  2. dry with materialThe extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customEA flushed
  6. washto elute DIEA

Sources & evidence

ORD record
ord-108951f80c3a41cd9b97bba1d6171445
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

Loading…