Diisopropylethylamine → 2-(4-chlorophenyl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one dihydrochloride

HRID 1675847Notes

Reaction equation

HRID 1675847 reaction equation
CCN(C(C)C)C(C)C.[ClH:10].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.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([CH2:39][N:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)[C:36](O)=[O:37])=[CH:31][CH:30]=1.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>[ClH:28].[ClH:10].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([CH2:39][N:40]2[CH2:41][CH2:42][CH2:43][CH2:44]2)[C:36]([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:37])=[CH:31][CH:30]=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 673399992-(4-Chlorophenyl)-3-(pyrrolidin-1-yl)propanoic acid

Product 1

HCID 247823152-(4-chlorophenyl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one dihydrochlorideYield 27.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (44.4 mg, 0.343 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), 2-(4-chlorophenyl)-3-(pyrrolidin-1-yl)propanoic acid (59.8 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 for 5 days, 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), and eluted by a mixture of MeOH and CH2Cl2 (3:97 to 5:95) to give 2-(4-chlorophenyl)-1-(4-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(pyrrolidin-1-yl)propan-1-one dihydrochloride (6 mg, 17%) as an off-white solid.

Workup

  1. washwashed with saturated aqueous NaHCO3
  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 MeOH and CH2Cl2 (3:97 to 5:95)

Sources & evidence

ORD record
ord-630b8962c0ef4b2c86087ae9f3cb642f
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

Loading…