Triethylamine → HCID 25108833, compound

HRID 2381152Notes

Reaction equation

HRID 2381152 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[F:32][C:33]1[CH:51]=[C:50]([I:52])[CH:49]=[CH:48][C:34]=1[CH2:35][N:36]1[C:40]2=[CH:41][N:42]=[CH:43][CH:44]=[C:39]2[CH:38]=[C:37]1[C:45]([O-:47])=O.[Na+].Cl.[CH:55]1([CH2:58][O:59][NH2:60])[CH2:57][CH2:56]1>CN(C=O)C.C(OCC)(=O)C>[CH:55]1([CH2:58][O:59][NH:60][C:45]([C:37]2[N:36]([CH2:35][C:34]3[CH:48]=[CH:49][C:50]([I:52])=[CH:51][C:33]=3[F:32])[C:40]3=[CH:41][N:42]=[CH:43][CH:44]=[C:39]3[CH:38]=2)=[O:47])[CH2:57][CH2:56]1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 11557279O-(cyclopropylmethyl)hydroxylamine hydrochloride2×HCID 68484005HCID 68484005, compound

Product 1

HCID 25108833HCID 25108833, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (67 mg, 0.18 mmol) and triethylamine (50 μL, 0.35 mmol) were added to a solution of sodium 1-(2-fluoro-4-iodo-benzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (49 mg, 0.12 mmol) and O-cyclopropylmethyl-hydroxylamine hydrochloride (21.8 mg, 0.178 mmol) in DMF (500 μL). The reaction mixture was stirred at room temperature for 18 h, then a further 11 mg (0.09 mmol) of O-cyclopropylmethyl-hydroxylamine hydrochloride, 33 mg (0.09 mmol) of HATU, and 50 μL (0.35 mmol) of triethylamine was added. Stirring was continued for a further 18 h, then the reaction mixture was poured into ethyl acetate (15 mL). The organic layer was washed with a 1:1 solution of saturated NaHCO3 and brine (10 mL), dried over Na2SO4, filtered and concentrated to afford a yellow oil. The crude product was purified by reversed phase HPLC to afford the title compound as a white powder (TFA salt, 39 mg, 57%). LCMS (Method C): RT=3.17 min, M+H+=466. 1H NMR (DMSO-D6): δ=0.21 (m, 2H), 0.51 (m, 2H), 1.00 (m, 1H), 3.60 (d, J=7.2 Hz, 2H), 5.96 (s, 2H), 6.61 (t, J=8.0 Hz, 1H), 7.33 (s, 1H), 7.47 (dd, J=8.0, 1.2 Hz, 1H), 7.68 (dd, J=9.6, 1.6 Hz, 1H), 8.24 (d, J=6.4 Hz, 1H), 8.43 (d, J=6.4 Hz, 1H), 9.52 (s, 1H).

Workup

  1. stirringStirring
  2. waitwas continued for a further 18 h
  3. washThe organic layer was washed with a 1:1 solution of saturated NaHCO3 and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow oil
  8. customThe crude product was purified by reversed phase HPLC

Sources & evidence

ORD record
ord-eca9bef6dfb04281809b742c5a1bfa80
Source dataset
uspto-grants-2012_09
Patent number
US08258152B2

Reaction notes

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