Lithium Hydroxide → (S)-{2-(4-Chlorobenzyl)-3-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-oxo-propyl}-carbamic acid tert-butyl ester

HRID 1192358Notes

Reaction equation

HRID 1192358 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.C1(S([N:21]2[C:25]3[N:26]=[CH:27][N:28]=[C:29]([N:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[C:24]=3[C:23]([CH3:36])=[CH:22]2)(=O)=O)C=CC=CC=1.[C:37]([O:41][C:42]([NH:44][CH2:45][C@H:46]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=1)[C:47](O)=[O:48])=[O:43])([CH3:40])([CH3:39])[CH3:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Li+].[OH-]>C(Cl)Cl.C([O-])(O)=O.[Na+].CO>[C:37]([O:41][C:42](=[O:43])[NH:44][CH2:45][C@H:46]([CH2:50][C:51]1[CH:52]=[CH:53][C:54]([Cl:57])=[CH:55][CH:56]=1)[C:47]([N:33]1[CH2:32][CH2:31][N:30]([C:29]2[C:24]3[C:23]([CH3:36])=[CH:22][NH:21][C:25]=3[N:26]=[CH:27][N:28]=2)[CH2:35][CH2:34]1)=[O:48])([CH3:40])([CH3:38])[CH3:39]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 40153909(S)-3-((Tert-butoxycarbonyl)amino)-2-(4-chlorobenzyl)propanoic acidHCID 675377857-Benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride

Product 1

HCID 69811844(S)-{2-(4-Chlorobenzyl)-3-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-oxo-propyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

DIPEA (120 μL, 0.70 mmol) was added to a suspension of 7-Benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (50 mg, 0.12 mmol) and (S)-2-(tert-Butoxycarbonylamino-methyl)-3-(4-chlorophenyl)-propionic acid (40 mg, 0.13 mmol) in DCM (10 mL) at room temperature. Then, HBTU (48 mg, 0.13 mmol) was added and the reaction stirred at room temperature overnight. MeOH (5 mL) and 3M LiOH (1.2 mL) were added and the mixture stirred and heated at 50° C. for 2 hours. The mixture was diluted with saturated aqueous NaHCO3 (10 mL), extracted into DCM, dried over Na2SO4 and concentrated in vacuo. The crude mixture was purified by column chromatography on silica (50% EtOAc/hexanes) to give (S)-{2-(4-Chlorobenzyl)-3-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-3-oxo-propyl}-carbamic acid tert-butyl ester. LCMS (APCI+) m/z 253 [M+H]+; Rt: 2.85 min. This was taken up into MeOH (10 mL) and treated with anhydrous HCl (4M in dioxane, 20 mL.) The solution was stirred at room temperature overnight and concentrated in vacuo to give (S)-2-Aminomethyl-3-(4-chlorophenyl)-1-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride (21 mg, 37%.) LCMS (APCI+) m/z 413 [M+H]+; Rt: 1.82 min.

Workup

  1. stirringthe mixture stirred
  2. temperatureheated at 50° C. for 2 hours
  3. extractionextracted into DCM
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by column chromatography on silica (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a3011e7e547a41b4b44ad527500b7b26
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…