Sodium t-butoxide → HCID 78322868, compound

HRID 55863Notes

Reaction equation

HRID 55863 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][C:11]([N:16]3[CH2:20][CH2:19][C@H:18]([F:21])[CH2:17]3)=[C:12]([CH:15]=2)[C:13]#[N:14])[CH:5]=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH:36]=[CH:37][CH:38]=1)[C:26]([NH:28][CH:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)=[O:27].CC([O-])(C)C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([C:12]1[CH:15]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:22][C:23]3[CH:24]=[C:25]([CH:36]=[CH:37][CH:38]=3)[C:26]([NH:28][CH:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[O:27])[N:7]=2)[CH:9]=[N:10][C:11]=1[N:16]1[CH2:20][CH2:19][C@H:18]([F:21])[CH2:17]1)#[N:14]

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 433732833-amino-N-(1-methyl-piperidin-4-yl)-benzamideHCID 903695215-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

Product 1

HCID 78322868HCID 78322868, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

5-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile (8) (100 mg, 0.329 mmol), 3-amino-N-(1-methyl-piperidin-4-yl)-benzamide (115 mg, 0.493 mmol), Pd2(dba)3 (30 mg, 0.0327 mmol), NaOtBu (48 mg, 0.499 mmol) and Dave-Phos (130 mg, 0.330 mmol) were dissolved in 1,4-dioxane (3 mL). Nitrogen was bubbled through the stirred mixture for 5 minutes. The reaction mixture was then stirred at 120° C. in the microwave (250 W, stirring) for 2 hours. The solvent was evaporated in vacuo and the residue dissolved in DMSO (3 mL). The crude product was purified by reversed phase preparative LC-MS. Fractions containing desired product were combined and the MeOH evaporated in vacuo. The aqueous solution was frozen (−78° C.) and the solvent evaporated in vacuo (freeze dried). The title compound was obtained as an off-white solid (68 mg, 38%); LCMS, Rt=4.94 min (Method A), m/z 501 (MH+).

Workup

  1. customNitrogen was bubbled through the stirred mixture for 5 minutes
  2. customThe solvent was evaporated in vacuo
  3. dissolutionthe residue dissolved in DMSO (3 mL)
  4. customThe crude product was purified by reversed phase preparative LC-MS
  5. additionFractions containing desired product
  6. customthe MeOH evaporated in vacuo
  7. temperatureThe aqueous solution was frozen (−78° C.)
  8. customthe solvent evaporated in vacuo (freeze dried)

Sources & evidence

ORD record
ord-2479cdd4c4c949f8a4b485a577c599ea
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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