4-(7-Benzenesulfonyl-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester → 4-(7-Benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1192356

Reaction equation

HRID 1192356 reaction equation
[CH3:1][Zn]Cl.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[C:25](Br)=[CH:24][N:23]([S:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)(=[O:29])=[O:28])[C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[C:25]([CH3:1])=[CH:24][N:23]([S:27]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)(=[O:29])=[O:28])[C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 2

HCID 675395734-(7-Benzenesulfonyl-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl esterHCID 178477798HCID 178477798, compound

Product 1

HCID 675398494-(7-Benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 95.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

MeZnCl (2.0M in THF, 720 uL, 1.4 mmol) was added to a stirred solution 4-(7-Benzenesulfonyl-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (250 mg, 0.48 mmol) and tetrakis(triphenylphosphine)palladium(0) (140 mg, 0.12 mmol) in THF (10 mL) at room temperature under N2. The solution was stirred and heated at reflux for 2 hours, cooled to room temperature, quenched with saturated aqueous NH4Cl, extracted into EtOAc (2×100 mL), dried over Na2SO4 and concentrated in vacuo. The product was purified on a Biotage (silica, 40% EtOAc/hexanes) to give 4-(7-Benzenesulfonyl-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (210 mg, 94%.) LCMS (APCI+) m/z 458 [M+H]+; Rt: 3.73. 1H NMR (CDCl3, 400 MHz) δ 8.49 (1H, s), 8.18 (2H, d, J 8.2 Hz), 7.59 (1H, t, J 6.9 Hz), 7.50 (2H, t, J 7.8 Hz), 7.34 (1H, s), 3.59-3.54 (4H, m), 3.48-3.44 (4H, m), 2.35 (3H, s), 1.48 (9H, s.)

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. customquenched with saturated aqueous NH4Cl
  4. extractionextracted into EtOAc (2×100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe product was purified on a Biotage (silica, 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c74d42dfe80449169c61e96cb05537f6
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Linked notes

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