Hydrochloric Acid → HCID 59596583, compound

HRID 2264981Notes

Reaction equation

HRID 2264981 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][C:20]#[C:21][CH2:22][O:23]C2CCCCO2)[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:30][C:31]1[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=1[F:38])=[O:9])=C.Cl.O1CCOCC1>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][C:20]#[C:21][CH2:22][OH:23])[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:30][C:31]1[CH:36]=[CH:35][C:34]([I:37])=[CH:33][C:32]=1[F:38])=[O:9]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59596626HCID 59596626, compound

Product 1

HCID 59596583HCID 59596583, compoundYield 36.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 3-(2-fluoro-4-iodo-phenylamino)-1-[4-(tetrahydro-pyran-2-yloxy)-but-2-ynyl]-1-H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (47.0 mg, 0.075 mmol) in anhydrous MeOH (3.0 mL) under N2 was added 4 M HCl in dioxane (0.10 mL, 0.40 mmol, 5.5 eq), and the reaction mixture was stirred at room temperature. After 3 h the solvent was removed in vacuo and the residue was redissolved in acetonitrile (2.0 mL) and loaded onto Phenomenex Strata-X cartridge (5 g). The cartridge was washed with water (10 mL) and methanol (15 ml). The desired product was then eluted using 2M ammonia in MeOH. Trituration from DCM-hexane afforded the title compound as a yellow solid (14.1 mg, 36.3%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.66 (broad s, 1H), 8.58 (s, 1H), 8.36 (d, J=5.86 Hz, 1H), 7.70 (d, J=6.8 Hz, 1H), 7.63 (m, 1H), 7.55 (dd, J=11.03, 1.6 Hz, 1H), 7.26-7.17 (m, 1H), 6.23 (t, J=8.8 Hz, 1H), 5.35 (s, 2H), 5.18 (t, J=5.96 Hz, 1H), 4.80-4.74 (m, 1H), 4.02 (d, J=4.25 Hz, 2H), 3.85 (t, J=4.76 Hz, 2H), 3.60-3.48 (m, 2H); LC-MS (method D): [M+H]+=525.1, RT=1.59 min.

Workup

  1. customAfter 3 h the solvent was removed in vacuo
  2. dissolutionthe residue was redissolved in acetonitrile (2.0 mL)
  3. washThe cartridge was washed with water (10 mL) and methanol (15 ml)
  4. washThe desired product was then eluted

Sources & evidence

ORD record
ord-59416bac27784a1dbda4a97190a14e95
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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