Lithium Hydroxide → 3-Boc-amino-2-(4-chlorophenyl)-1-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one

HRID 1192411Notes

Reaction equation

HRID 1192411 reaction equation
Cl.Cl.C1(S([N:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[C:15]=3[C:14]([CH3:27])=[CH:13]2)(=O)=O)C=CC=CC=1.[C:28]([CH2:35][C:36]([NH2:47])([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)[C:37](O)=[O:38])([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Li+].[OH-].C([O-])(O)=O.[Na+]>CO>[C:28]([CH2:35][C:36]([NH2:47])([C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=1)[C:37]([N:24]1[CH2:23][CH2:22][N:21]([C:20]2[C:15]3[C:14]([CH3:27])=[CH:13][NH:12][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:26][CH2:25]1)=[O:38])([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29]

Participants

7

Reactant 5

HCID 3939Lithium HydroxideHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 215841133-Boc-amino-2-(4-chlorophenyl)-propionic acidHCID 675377857-Benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride

Product 1

HCID 675403593-Boc-amino-2-(4-chlorophenyl)-1-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 7-benzenesulfonyl-5-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (35 mg. 0.081 mmol), 3-Boc-amino-2-(4-chlorophenyl)-propionic acid (27 mg, 0.089 mmol), and TEA (0.11 mL, 0.81 mmol) 1.2 mL DCM was added HBTU (34 mg, 0.089 mmol). The reaction mixture was stirred at room temperature 2 hours, after which 0.15 mL 3M LiOH and 1.0 mL MeOH were added. The reaction mixture was stirred at 35° C. for 3.5 hours, after which saturated NaHCO3 was added. The mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (flushed with 1:1 DCM:EtOAc, then gradient to 1:4 DCM:EtOAc) to give 3-Boc-amino-2-(4-chlorophenyl)-1-[4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one, which was used in the next step.

Workup

  1. stirringThe reaction mixture was stirred at 35° C. for 3.5 hours
  2. extractionThe mixture was extracted with DCM
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified on silica gel (
  7. customflushed with 1:1 DCM

Sources & evidence

ORD record
ord-ee9df9b45b1f42ea985fea10d8f2cf74
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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