Diisopropylethylamine → 3-(4-Cyclopropyl-2-fluoro-phenylamino)1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2264992Notes

Reaction equation

HRID 2264992 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:15]4[CH:16]=[N:17][CH:18]=[CH:19][C:14]=4[N:13]([CH3:20])[C:12]=3[C:21]([OH:23])=O)=[C:6]([F:24])[CH:5]=2)[CH2:3][CH2:2]1.[CH:25]([O:27][CH2:28][CH2:29][O:30][NH2:31])=[CH2:26].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>C1COCC1>[CH:25]([O:27][CH2:28][CH2:29][O:30][NH:31][C:21]([C:12]1[N:13]([CH3:20])[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:11]=1[NH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]=1[F:24])=[O:23])=[CH2:26]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595964403-(4-Cyclopropyl-2-fluoro-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

Product 1

HCID 595965283-(4-Cyclopropyl-2-fluoro-phenylamino)1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 33.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 3-(4-cyclopropyl-2-fluoro-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (88 mg, 0.25 mmol), O-(2-vinyloxy-ethyl)-hydroxylamine (028 mg, 0.28 mmol), HATU (114 mg, 0.30 mmol) and DIPEA (0.052 ml, 0.30 mmol) in THF (3 ml) was stirred at ambient temperature for 18 hours. On completion of the reaction, the mixture was concentrated in vacuo then re-dissolved in DCM. The solution was washed with saturated aqueous NaHCO3 and brine, dried over magnesium sulphate then concentrated in vacuo. The resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10) to give a yellow solid (34 mg, 33%). LCMS (method B): RT=2.46 min, M+H+=411. 1H NMR (CDCl3): 8.58 (1H, s), 8.41-8.36 (1H, m), 7.30 (1H, d, J=6.08 Hz), 7.26 (1H, d, J=1.99 Hz), 6.87 (1H, dd, J=8.33, 2.02 Hz), 6.47 (1H, dd, J=8.34, 3.82 Hz), 5.85 (1H, s), 4.11 (3H, s), 3.97-3.90 (2H, m), 3.71 (2H, dd, J=5.23, 3.41 Hz), 2.78 (1H, m), 1.22-1.13 (6H, m).

Workup

  1. customOn completion of the reaction
  2. concentrationthe mixture was concentrated in vacuo
  3. dissolutionthen re-dissolved in DCM
  4. washThe solution was washed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over magnesium sulphate
  6. concentrationthen concentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10)

Sources & evidence

ORD record
ord-c1a1d7dbc0754ad5a07a2dd7a1e09937
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…