Potassium Phosphate, Tribasic → 4-({(3S)-4-[(6-cyclopropyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

HRID 43429Notes

Reaction equation

HRID 43429 reaction equation
I[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([S:16]([C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=3[CH3:27])(=[O:18])=[O:17])[CH2:12][C@@H:11]2[CH3:28])=[O:9])=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:37]1(B(O)O)[CH2:39][CH2:38]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:37]1([C:2]2[N:7]=[CH:6][C:5]([C:8]([N:10]3[CH2:15][CH2:14][N:13]([S:16]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=4[CH3:27])(=[O:18])=[O:17])[CH2:12][C@@H:11]3[CH3:28])=[O:9])=[CH:4][CH:3]=2)[CH2:39][CH2:38]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 591613364-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

Product 1

HCID 591613704-({(3S)-4-[(6-cyclopropyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrileYield 2.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Argon was bubbled through a solution of 4-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile (50.0 mg, 0.098 mmol) (may be prepared as described in Example 50), potassium phosphate (72.8 mg, 0.343 mmol) and cyclopropylboronic acid (25.2 mg, 0.294 mmol) in toluene (3 mL) and water (200 μl) for 30 min. Tricyclohexylphosphine (2.75 mg, 9.80 μmol) and palladium(II)acetate (1.100 mg, 4.90 μmol) were added and the resulting pale yellow solution heated at 100° C. for 2 h. LCMS had not changed from 1 min, at 45° C. The solution was cooled and concentrated under vacuum to leave a pale yellow solid. Purification by MDAP and concentration of the desired fractions gave the title compound (1.0 mg) as a clear film, and a batch of recovered 4-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile (28.2 mg) starting material.

Workup

  1. temperatureThe solution was cooled
  2. concentrationconcentrated under vacuum
  3. customto leave a pale yellow solid
  4. customPurification by MDAP and concentration of the desired fractions

Sources & evidence

ORD record
ord-34b8e156a62b4199b3f53fb1ab552694
Source dataset
uspto-grants-2013_09
Patent number
US08536183B2

Reaction notes

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