Diisopropylethylamine → HCID 66845588, compound

HRID 1916395Notes

Reaction equation

HRID 1916395 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:26][C@H:27]1[C:35]2[C:34]([N:36]3[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)=[N:33][CH:32]=[N:31][C:30]=2[C@H:29]([OH:42])[CH2:28]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C@@H:13]([C@@H:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:14]([N:39]2[CH2:40][CH2:41][N:36]([C:34]3[C:35]4[C@H:27]([CH3:26])[CH2:28][C@@H:29]([OH:42])[C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:37][CH2:38]2)=[O:15])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564918(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acidHCID 66618034(5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride

Product 1

HCID 66845588HCID 66845588, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (0.1765 g, 0.5194 mmol) was combined with (5R,7R)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (0.1596 g, 0.5194 mmol) and then slurried in methylene chloride (4.5 mL). The suspension was treated with diisopropylethylamine (0.2714 mL, 1.558 mmol) then with HBTU (0.1970 g, 0.5194 mmol), and the mixture was stirred at ambient temperature for 16 hours. The reaction was quenched with 10% Na2CO3 and then separated. The aqueous portion was washed twice with dichloromethane. The combined organic portions were dried with Na2SO4 and concentrated in vacuo. The residue was subjected to chromatography on SiO2 eluting with 4% MeOH/dichloromethane to yield (S)-tert-butyl 2-((S)-1-(4-chlorophenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (0.256 g, 89%). MS (ESI+) [M+H] 556.1/558.1.

Workup

  1. customThe reaction was quenched with 10% Na2CO3
  2. customseparated
  3. washThe aqueous portion was washed twice with dichloromethane
  4. dry with materialThe combined organic portions were dried with Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-22ae0e6a23ce46e38d76a41c689aa63c
Source dataset
uspto-grants-2013_12
Patent number
US08618097B2

Reaction notes

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