Diisopropylethylamine → 4-({(3S)-4-[(6-Chloro-2-methyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

HRID 2066139Notes

Reaction equation

HRID 2066139 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[C:29]([C:33]([OH:35])=O)=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.[CH3:45][C:46]1[CH:47]=[C:48]([CH:51]=[CH:52][C:53]=1[S:54]([N:57]1[CH2:62][CH2:61][NH:60][C@@H:59]([CH3:63])[CH2:58]1)(=[O:56])=[O:55])[C:49]#[N:50]>CN(C=O)C>[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[C:29]([C:33]([N:60]2[CH2:61][CH2:62][N:57]([S:54]([C:53]3[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][C:46]=3[CH3:45])(=[O:56])=[O:55])[CH2:58][C@@H:59]2[CH3:63])=[O:35])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 462238396-Chloro-2-methylpyridine-3-carboxylic acidHCID 591520673-Methyl-4-{[(3S)-3-methyl-1-piperazinyl]sulfonyl}benzonitrile

Product 1

HCID 591613924-({(3S)-4-[(6-Chloro-2-methyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

HATU (425 mg, 1.12 mmol) was added to a solution of 6-chloro-2-methyl-3-pyridinecarboxylic acid (commercially available, e.g. from Anichem, or may be prepared according to known methods) (160 mg, 0.93 mmol) in DMF (3 ml) and the mixture was treated with DIPEA (0.407 ml, 2.33 mmol). This mixture was stirred for ca. 10 min at ambient temperature. 3-Methyl-4-{[(3S)-3-methyl-1-piperazinyl]sulfonyl}benzonitrile (may be prepared as described in Description 11) (313 mg, 1.12 mmol) was added as a solution in DMF (2 ml) and stirring was continued for ca. 1 hour. The reaction mixture was partitioned between DCM and sat aq. NaHCO3 solution (20 ml each). The layers were separated and the aqueous was washed with further DCM (2×20 ml). The combined organic layers were dried (hydrophobic frit) and concentrated to leave a dark brown gum. Purification by silica chromatography (Biotage SP4, 25S cartridge), eluting with 12-100% ethyl acetate in isohexane, gave the title compound as a pale cream foam (376 mg).

Workup

  1. custommay be prepared
  2. stirringstirring
  3. waitwas continued for ca. 1 hour
  4. customThe reaction mixture was partitioned between DCM
  5. customThe layers were separated
  6. washthe aqueous was washed with further DCM (2×20 ml)
  7. customThe combined organic layers were dried (hydrophobic frit)
  8. concentrationconcentrated
  9. customto leave a dark brown gum
  10. customPurification by silica chromatography (Biotage SP4, 25S cartridge)
  11. washeluting with 12-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-f034cca2420b48108e3e922182a95a07
Source dataset
uspto-grants-2012_10
Patent number
US08288388B2

Reaction notes

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