Trifluoroacetic acid → HCID 90403472, compound

HRID 1049366Notes

Reaction equation

HRID 1049366 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30])=[N:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)=[CH:11][CH:10]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:35])([CH3:34])[CH3:36])=[O:30])=[N:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90403157HCID 90403157, compound

Product 1

HCID 90403472HCID 90403472, compoundYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N-((5-((6′-(bis(tert-butoxycarbonyl)amino)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (0.23 g, 0.379 mmol) and TFA (0.44 mL, 5.7 mmol) in DCM (4 mL) was stirred at RT for 16 h. The mixture was concentrated to dryness, treated with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-((5-((6′-amino-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (125 mg, 81%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.21 (s, 1H), 10.45 (br s, 1H), 8.62 (d, J=2.5 Hz, 1H), 8.44 (d, J=5.7 Hz, 1H), 8.27 (d, J=2.9 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H), 8.01 (dd, J=8.7, 2.5 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.38 (d, J=2.4 Hz, 1H), 6.74 (dd, J=5.7, 2.4 Hz, 1H), 6.47 (d, J=8.7 Hz, 1H), 6.27 (d, J=4.7 Hz, 2H), 1.21 (s, 9H); MS (ESI) m/z: 407.2 (M+H+).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additiontreated with satd
  3. extractionNaHCO3 and extracted with EtOAc (2×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-a5b1cd9f050d496b843630a2573ffe3a
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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