Trifluoroacetic acid → HCID 86644904, compound

HRID 1874987Notes

Reaction equation

HRID 1874987 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:34][CH2:35][C:36]1[C:37]([F:53])=[C:38]([O:43][C:44]2[CH:45]=[C:46]([CH:49]=[C:50]([Cl:52])[CH:51]=2)[C:47]#[N:48])[C:39]([Cl:42])=[CH:40][CH:41]=1.C[Si](C)(C)CCOC[N:60]1[C:64]2[CH:65]=[C:66]([C:68](O)=[O:69])[NH:67][C:63]=2[N:62]=[CH:61]1.[C:73]([OH:79])([C:75]([F:78])([F:77])[F:76])=[O:74]>CN(C=O)C.C(Cl)Cl>[F:76][C:75]([F:78])([F:77])[C:73]([OH:79])=[O:74].[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][NH:34][C:68]([C:66]2[NH:67][C:63]3[N:62]=[CH:61][NH:60][C:64]=3[CH:65]=2)=[O:69])=[C:37]([F:53])[C:38]=1[O:43][C:44]1[CH:45]=[C:46]([C:47]#[N:48])[CH:49]=[C:50]([Cl:52])[CH:51]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 68487214HCID 68487214, compound

Product 1

HCID 86644904HCID 86644904, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

HATU (0.092 g, 0.241 mmol) was added to a solution of DIPEA (0.042 ml, 0.241 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol) and 1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylic acid (0.045 g, 0.161 mmol) dissolved in DMF (2 ml). The resulting solution was stirred overnight. The reaction mixture was partitioned between water and EtOAc. The organic layer was separated, dried over MgSO4 and evaporated to a residue. Purification was accomplished by reverse-phase HPLC (water/acetonitrile with 0.1% TFA) to afford a residue which was dissolved in DCM and TFA. This was stirred until LCMS showed complete removal of the SEM group. The solvent and acid were evaporated and the resulting solid washed with DCM and acetone to afford the title compound (0.0052 g, 6%) as a tan solid. 1H NMR (400 MHz, CD3OD) δ ppm 8.65 (s, 1H), 7.55 (t, 1H), 7.36-7.43 (m, 2H), 7.27 (t, 1H), 7.20 (dd, 1H), 6.95 (s, 1H), 4.63 (s, 2H). 19F NMR (376 MHz, CD3OD) δ ppm −77.52 (s, 3F), −133.01 (s, 1F). LCMS: m/z=442.0 (M−1).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated to a residue
  5. customPurification
  6. customto afford a residue which
  7. stirringThis was stirred until LCMS
  8. customremoval of the SEM group
  9. customThe solvent and acid were evaporated
  10. washthe resulting solid washed with DCM and acetone

Sources & evidence

ORD record
ord-d3b73530b7b04ee089bf00298c9c538c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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