Lithium Hydroxide → 2-[5-(4-tert-Butoxycarbonyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

HRID 2189335Notes

Reaction equation

HRID 2189335 reaction equation
C[O:2][C:3]([C:5]1[N:33]([CH:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[C:6]=1[CH3:39])=[O:4].[OH-].[Li+]>CO.O.C(Cl)Cl.O>[C:29]([O:28][C:26]([N:23]1[CH2:24][CH2:25][N:20]([C:17]2[CH:18]=[CH:19][C:14]([NH:13][C:10]3[N:11]=[CH:12][C:7]4[C:6]([CH3:39])=[C:5]([C:3]([OH:4])=[O:2])[N:33]([CH:34]5[CH2:35][CH2:36][CH2:37][CH2:38]5)[C:8]=4[N:9]=3)=[N:15][CH:16]=2)[CH2:21][CH2:22]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 69079901HCID 69079901, compound

Product 1

HCID 580160322-[5-(4-tert-Butoxycarbonyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acidYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21958822Dichloromethane methanol waterSolvent

Procedure

To a suspension of 2-[5-(4-tert-Butoxycarbonyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester (250 mg, 0.467 mmol) (prepared as described in the procedure for the synthesis of Example 384), in MeOH/H2O/DCM (70 mL) is added a solution of lithium hydroxide (39.2 mg, 0.93 mmol) in water (15 mL). The reaction mixture is heated to reflux for 4 hours. The reaction mixture is allowed to cool to room temperature and concentrated in vacuo. The resulting solution is acidified to pH˜3 using saturated aqueous citric acid solution. The solution is evaporated and the residue is purified by preparative HPLC to give 2-[5-(4-tert-Butoxycarbonyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid as a yellow solid (105 mg, 53%). [M+H]+=522.3

Workup

  1. customprepared
  2. temperatureThe reaction mixture is heated
  3. temperatureto reflux for 4 hours
  4. concentrationconcentrated in vacuo
  5. customThe solution is evaporated
  6. customthe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-d3de051fd5c24860b430732cbcb5f537
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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