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 1675862Notes

Reaction equation

HRID 1675862 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-075624219e5c4a329b3dd8c77c51005e
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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