4-Methylmorpholine → N-(2-{[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}-2-methylcyclopentyl)-3-(pyrimidin-2-yl)pyridine-2-carboxamide

HRID 1750705Notes

Reaction equation

HRID 1750705 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2([CH3:19])[CH2:17][CH2:16][CH2:15][CH:14]2[NH2:18])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CN1CCOCC1.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.[N:49]1[CH:54]=[CH:53][CH:52]=[N:51][C:50]=1[C:55]1[C:56]([C:61](O)=[O:62])=[N:57][CH:58]=[CH:59][CH:60]=1>C(#N)C.C(Cl)Cl>[F:1][C:2]1[C:3]([NH:12][C:13]2([CH3:19])[CH2:17][CH2:16][CH2:15][CH:14]2[NH:18][C:61]([C:56]2[C:55]([C:50]3[N:49]=[CH:54][CH:53]=[CH:52][N:51]=3)=[CH:60][CH:59]=[CH:58][N:57]=2)=[O:62])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 593636623-(Pyrimidin-2-yl)pyridine-2-carboxylic acidHCID 1183080491-N-[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]-1-methylcyclopentane-1,2-diamine2×

Product 1

HCID 118308302N-(2-{[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}-2-methylcyclopentyl)-3-(pyrimidin-2-yl)pyridine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-N-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]-1-methylcyclopentane-1,2-diamine (Intermediate 28; 0.225 g, 0.81 mmol) and 4-methylmorpholine (0.134 ml, 1.217 mmol) in acetonitrile (5 ml) was added TOTU (0.399 g, 1.23 mmol) and 3-(pyrimidin-2-yl)pyridine-2-carboxylic acid (CAS number 1228431-21-7; 0.163 g, 0.81 mmol). The reaction was stirred at room temperature for 1 hour and then was diluted with DCM and washed with brine. The organics were dried over magnesium sulfate, concentrated in vacuo and purified by SCX chromatography (2M ammonia in methanol). The resulting residue was purified by column chromatography (silica, 0-10% methanol/DCM) and further purified by reverse phase chromatography (C18 silica, 5-95% water (0.05% ammonia)/acetonitrile) to afford the title compound.

Workup

  1. washwashed with brine
  2. dry with materialThe organics were dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. custompurified by SCX chromatography (2M ammonia in methanol)
  5. customThe resulting residue was purified by column chromatography (silica, 0-10% methanol/DCM)
  6. customfurther purified by reverse phase chromatography (C18 silica, 5-95% water (0.05% ammonia)/acetonitrile)

Sources & evidence

ORD record
ord-3f6ff561aaa4475d884139927a921ba0
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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