Diisopropylethylamine → (RS)-5-chloro-pyridine-2-carboxylic acid [3-(3-cyclopropyl-5-thioxo-morpholin-3-yl)-4-fluoro-phenyl]-amide

HRID 1929504Notes

Reaction equation

HRID 1929504 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH2:44][C:45]1[CH:46]=[CH:47][C:48]([F:61])=[C:49]([C:51]2([CH:58]3[CH2:60][CH2:59]3)[NH:56][C:55](=[S:57])[CH2:54][O:53][CH2:52]2)[CH:50]=1.C(=O)([O-])O.[Na+]>ClCCl>[CH:58]1([C:51]2([C:49]3[CH:50]=[C:45]([NH:44][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=4)=[O:10])[CH:46]=[CH:47][C:48]=3[F:61])[CH2:52][O:53][CH2:54][C:55](=[S:57])[NH:56]2)[CH2:60][CH2:59]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27628725-Chloro-2-picolinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58155241HCID 58155241, compound

Product 1

HCID 86651226(RS)-5-chloro-pyridine-2-carboxylic acid [3-(3-cyclopropyl-5-thioxo-morpholin-3-yl)-4-fluoro-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-chloro-pyridine-2-carboxylic acid (0.136 g, 0.86 mmol) in dichloromethane (15 ml), was treated with Huenig's base (0.30 ml, 1.73 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (0.328 g, 0.86 mmol) at room temperature. After 15 minutes of stirring, (RS)-5-(5-amino-2-fluoro-phenyl)-5-cyclopropyl-morpholine-3-thione (0.177 g, 0.66 mmol) was added and stirring continued for one hour. For the workup, the light yellow solution was poured on an ice-cold saturated solution of sodium hydrogen-carbonate, then extracted twice with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel using a 9:1-mixture of dichloromethane and ethyl acetate as the eluent. The 5-Chloro-pyridine-2-carboxylic acid [3-((RS)-3-cyclopropyl-5-thioxo-morpholin-3-yl)-4-fluoro-phenyl]-amide was obtained as an off-white solid (0.245 g, 90% of theory). Mass (calculated) C19H17ClFN3O2S [405.879]; (found) [M+H]+=406.

Workup

  1. stirringstirring
  2. waitcontinued for one hour
  3. extractionextracted twice with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel using a 9

Sources & evidence

ORD record
ord-294e44bfe4b448af91331a05da2fd3b3
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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