Hydrochloric Acid → HCID 25131973, compound

HRID 2381154Notes

Reaction equation

HRID 2381154 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]#[CH:29])=[CH:24][C:23]=3[F:30])[C:15]3=[CH:16][N:17]=[CH:18][CH:19]=[C:14]3[CH:13]=2)=[O:11])[CH2:4][O:3]1.Cl>>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]#[CH:29])=[CH:24][C:23]=2[F:30])[C:15]2=[CH:16][N:17]=[CH:18][CH:19]=[C:14]2[CH:13]=1)=[O:11]

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 59452210HCID 59452210, compound

Product 1

HCID 25131973HCID 25131973, compoundYield 18.6%

Procedure

1-(4-Ethynyl-2-fluoro-benzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (30 mg, 0.07 mmol) was dissolved in 0.067 M methanolic HCl solution (3 ml, 0.20 mmol) and stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo then azeotroped with toluene (2×15 ml) to give a solid residue. Purification of the solid residue by flash chromatography (NH2-SPE, dichloromethane, ethyl acetate, 20:80 methanol:dichloromethane, 5:35:60 triethylamine:methanol: dichloromethane) followed by trituration in acetonitrile afforded the product as a cream solid (5 mg, 18%). LCMS (Method A): RT=4.03 min, (M−H)−=382, M+H+=384. 1H NMR (CD3OD): 3.58 (1H, s), 3.60 (2H, m), 3.85 (1H, m), 3.91 (1H, dd, J=10.2, 6.8 Hz), 4.03 (1H, dd, J=10.2, 3.8 Hz), 5.97 (2H, s), 6.84 (1H, t, J=7.9 Hz), 7.11 (1H, s), 7.16 (1H, dd, J=7.9, 1.5 Hz), 7.21 (1H, dd, J=10.8, 1.5 Hz), 7.76 (1H, d, J=5.6 Hz), 8.22 (1H, d, br, J=5.6 Hz), 8.93 (1H, s).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthen azeotroped with toluene (2×15 ml)
  3. customto give a solid residue
  4. customPurification of the solid residue by flash chromatography (NH2-SPE, dichloromethane, ethyl acetate, 20:80 methanol:dichloromethane, 5:35:60 triethylamine:methanol: dichloromethane)

Sources & evidence

ORD record
ord-6f4ba6f30f534bfd9413b4166371760b
Source dataset
uspto-grants-2012_09
Patent number
US08258152B2

Reaction notes

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