4-Aminopyridine → HCID 68032340, compound

HRID 1397168Notes

Reaction equation

HRID 1397168 reaction equation
FC(F)(F)C(OCC1C=CC=CC=1)=O.[NH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CS([C:35]1[N:40]=[C:39]([C:41]2[C:42]([C:48]([F:51])([F:50])[F:49])=[N:43][C:44]([NH2:47])=[N:45][CH:46]=2)[CH:38]=[CH:37][N:36]=1)=O>C1COCC1>[N:19]1[CH:20]=[CH:21][C:16]([NH:15][C:35]2[N:40]=[C:39]([C:41]3[C:42]([C:48]([F:49])([F:51])[F:50])=[N:43][C:44]([NH2:47])=[N:45][CH:46]=3)[CH:38]=[CH:37][N:36]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 17274-AminopyridineHCID 561775HCID 561775, compoundHCID 2733832Lithium HexamethyldisilazideHCID 67983786HCID 67983786, compound

Product 1

HCID 68032340HCID 68032340, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

This compound was synthesized in an analogous manner to 21 utilizing benzyl 2,2,2-trifluoroacetate in step 1. To a solution of 4-aminopyridine (17.38 mg, 0.185 mmol) in THF (92 μl) cooled to −78° C. under nitrogen, LiHMDS (852 μl, 0.852 mmol) was added dropwise. The reaction mixture was warmed up to rt, then was stirred for 30 minutes. To the reaction mixture cooled back to −78° C., 2-(methylsulfinyl)-4′-(trifluoromethyl)-4,5′-bipyrimidin-2′-amine (14 mg, 0.046 mmol) was added, and the reaction mixture was warmed up to rt, then was stirred for 1 hour. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product as a pale yellow solid (3.98 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.13 (d, J=4.52 Hz, 1 H) 7.67 (br. s., 2 H) 7.77 (d, J=6.02 Hz, 2 H) 8.34 (d, J=6.02 Hz, 2 H) 8.56-8.74 (m, 2 H) 10.23 (s, 1 H). HRMS (ES+) for C14 H10F3N7.H+ [MH+]: calcd, 334.1028. found, 334.1037. UV-LC: 97.31/100% UV purity at 214/254 nm; tR=2.47 minutes over 7.75 minutes.

Workup

  1. temperatureTo the reaction mixture cooled back to −78° C.
  2. temperaturethe reaction mixture was warmed up to rt
  3. stirringwas stirred for 1 hour
  4. customThe crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes]

Sources & evidence

ORD record
ord-a3fa5bf04a5949f2b5e0eece065701b5
Source dataset
uspto-grants-2014_12
Patent number
US08901147B2

Reaction notes

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