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

HRID 1675873Notes

Reaction equation

HRID 1675873 reaction equation
Cl.Cl.[F:3][C:4]1([F:20])[C:8]2[N:9]=[CH:10][N:11]=[C:12]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:7]=2[C@H:6]([CH3:19])[CH2:5]1.[C:21]([O:25][C:26]([N:28]([CH:41]([CH3:43])[CH3:42])[CH2:29][C@H:30]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)[C:31](O)=[O:32])=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CC(=O)OCC>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([C@H:30]([C:31]([N:16]2[CH2:17][CH2:18][N:13]([C:12]3[C:7]4[C@H:6]([CH3:19])[CH2:5][C:4]([F:3])([F:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:14][CH2:15]2)=[O:32])[CH2:29][N:28]([CH:41]([CH3:42])[CH3:43])[C:26](=[O:27])[O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:35][CH:36]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 66846210(R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride

Product 1

HCID 67338612tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateYield 68%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (R)-7,7-difluoro-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (0.015 g, 0.046 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.016 g, 0.046 mmol), and DIEA (0.024 ml, 0.14 mmol) in 1.7 mL DCM was added HBTU (0.017 g, 0.046 mmol). The reaction mixture was stirred 15 hours, after which 2M Na2CO3 was added. The mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 12S) by first flushing with about 120 mL 5:1 DCM:EA, then gradient to 1:1 DCM:EA to give tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((R)-7,7-difluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]-pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.018 g, 68% yield) as a white foam. MS (APCI)+ m/z 578 [M+H]+.

Workup

  1. extractionThe mixture was extracted with DCM
  2. dry with materialthe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude was purified on silica gel (Biotage 12S)
  6. customby first flushing with about 120 mL 5:1 DCM

Sources & evidence

ORD record
ord-05e1e50183784dc982450189ba7f1bd5
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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