Diisopropylethylamine → tert-butyl 3-(4-chlorophenyl)-3-methyl-4-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-4-oxobutylcarbamate

HRID 82379Notes

Reaction equation

HRID 82379 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[CH3:12][C@H:13]1[C:21]2[C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[N:19][CH:18]=[N:17][C:16]=2[CH2:15][CH2:14]1.[C:28]([O:32][C:33]([NH:35][CH2:36][CH2:37][C:38]([C:43]1[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=1)([CH3:42])[C:39](O)=[O:40])=[O:34])([CH3:31])([CH3:30])[CH3:29].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CCOC(C)=O>[Cl:49][C:46]1[CH:47]=[CH:48][C:43]([C:38]([CH3:42])([C:39]([N:25]2[CH2:26][CH2:27][N:22]([C:20]3[C:21]4[C@H:13]([CH3:12])[CH2:14][CH2:15][C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:23][CH2:24]2)=[O:40])[CH2:37][CH2:36][NH:35][C:33](=[O:34])[O:32][C:28]([CH3:30])([CH3:31])[CH3:29])=[CH:44][CH:45]=1

Participants

7

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 673403054-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)-2-methylbutanoic acid

Product 1

HCID 67340444tert-butyl 3-(4-chlorophenyl)-3-methyl-4-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-4-oxobutylcarbamateYield 74%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (35.5 mg, 0.275 mmol) was added to a suspension of (R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine dihydrochloride (20 mg, 0.69 mmol), 4-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)-2-methylbutanoic acid (27.0 mg, 0.082 mmol), and O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (31.3 mg, 0.082 mmol) in CH2Cl2 (5.0 mL) at room temperature. The resulting mixture was stirred overnight, diluted with EtOAc, washed with saturated aqueous NaHCO3 and saturated aqueous NH4Cl. The organic layer was dried (MgSO4) and concentrated. The residue was purified by a silica cartridge (5.0 g), eluted by a mixture of EtOAc and hexane (60:40) to give tert-butyl 3-(4-chlorophenyl)-3-methyl-4-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-4-oxobutylcarbamate as a clear oil (27 mg, 74%). LCMS (APCI+) [M+H]+ 528.1; Rt: 3.38 min.

Workup

  1. washwashed with saturated aqueous NaHCO3 and saturated aqueous NH4Cl
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by a silica cartridge (5.0 g)
  5. washeluted by a mixture of EtOAc and hexane (60:40)

Sources & evidence

ORD record
ord-b66b27f7bec648a396cc72b1a806b94f
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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