Diisopropylethylamine → HCID 66617992, compound

HRID 532787Notes

Reaction equation

HRID 532787 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[C:15]([CH3:29])([OH:28])[CH2:14]1.[C:30]([O:34][C:35]([N:37]([CH:50]([CH3:52])[CH3:51])[CH2:38][CH:39]([C:43]1[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=1)[C:40](O)=[O:41])=[O:36])([CH3:33])([CH3:32])[CH3:31].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[Cl:49][C:46]1[CH:47]=[CH:48][C:43]([CH:39]([C:40]([N:25]2[CH2:24][CH2:23][N:22]([C:20]3[C:21]4[C@H:13]([CH3:12])[CH2:14][C:15]([OH:28])([CH3:29])[C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:27][CH2:26]2)=[O:41])[CH2:38][N:37]([CH:50]([CH3:51])[CH3:52])[C:35](=[O:36])[O:34][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251786973-{[(tert-Butoxy)carbonyl](propan-2-yl)amino}-2-(4-chlorophenyl)propanoic acidHCID 66617865HCID 66617865, compound

Product 1

HCID 66617992HCID 66617992, compoundYield 100.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 4-((5R)-7-hydroxy-5,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (28 mg, 0.080 mmol) in DCM (6 mL) was added to a 4.0M HCl solution in dioxane (1.4 mL, 5.63 mmol). The mixture was stirred at room temperature for 4 hours. A 4.0M HCl solution in dioxane (1.4 mL, 5.63 mmol) from a different bottle was added. The resulting mixture was stirred for 18 hours. The solvents were removed in vacuo to give (5R)-5,7-dimethyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride. DIPEA (41.5 mg, 0.321 mmol) was added to a suspension of this (5R)-5,7-dimethyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (25.8 mg, 0.0803 mmol), 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (32.9 mg, 0.0964 mmol), and O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (36.6 mg, 0.0964 mmol) in CH2Cl2 (6 mL) at room temperature. The resulting mixture was stirred for 1 hour. The solvent was removed in vacuo. The residue was purified by a silica cartridge (5.0 g) eluted by EtOAc to give tert-butyl 2-(4-chlorophenyl)-3-(4-((5R)-7-hydroxy-5,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (46 mg, 100%) as a gel. LCMS (APCI+) [M−Boc+H] +472.2; Rt: 3.51 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customThe residue was purified by a silica cartridge (5.0 g)
  3. washeluted by EtOAc

Sources & evidence

ORD record
ord-c83bba98389e4b09ba6f3b6660c056c4
Source dataset
uspto-grants-2014_10
Patent number
US08853199B2

Reaction notes

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