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-oxopropyl(isopropyl)carbamate

HRID 1675845Notes

Reaction equation

HRID 1675845 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]([N:50]([CH:63]([CH3:65])[CH3:64])[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][N:50]([CH:63]([CH3:64])[CH3:65])[C:48](=[O:49])[O:47][C:43]([CH3:45])([CH3:44])[CH3:46])=[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 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acid

Product 1

HCID 67340744tert-butyl(S)-2-(4-chlorophenyl)-3-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateYield 101%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

HBTU (0.469 g, 1.24 mmol) was added to a solution of (R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (0.360 g, 1.24 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.423 g, 1.24 mmol), and DIEA (0.646 ml, 3.71 mmol) in DCM (8 mL). The reaction mixture was stirred at room temperature for 2 hours, after which 2M Na2CO3 was added. The reaction mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on a Biotage 40S (ca. 175 mL 4:1 DCM:EA flushed to elute DIEA, then gradient to 1:4 DCM:EA) 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-oxopropyl(isopropyl)carbamate (0.679 g, 101% yield) as a pale yellow syrup. LC/MS (APCI+) m/z 542.1 [M+H]+.

Workup

  1. extractionThe reaction mixture was extracted with DCM
  2. dry with materialthe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customEA flushed
  6. washto elute DIEA

Sources & evidence

ORD record
ord-ab84a92019ff46589fc311a3ed72bc61
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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