Hydrochloric Acid → HCID 67308696, compound

HRID 445210Notes

Reaction equation

HRID 445210 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8]([C:29]1[S:33][C:32]([C:34]([NH2:36])=O)=[CH:31][CH:30]=1)[CH:7]=[CH:6]2.P(Cl)(Cl)([Cl:39])=O.Cl>ClCCl>[ClH:39].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:18][CH:19]=1)=[C:8]([C:29]1[S:33][C:32]([C:34]#[N:36])=[CH:31][CH:30]=1)[CH:7]=[CH:6]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 58338549HCID 58338549, compound

Product 1

HCID 67308696HCID 67308696, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Add 5-(6-methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-2-carboxamide (79 mg, 0.16 mmol) and phosphoryl chloride (13 mL, 139.9 mmol) to a round bottom flask under nitrogen. Warm the resulting mixture to 100° C. and stir for 15 min. Cool the mixture to room temperature and concentrate in vacuo to give a yellow residue. Carefully quench the resulting residue with methanol and load onto an SCX acidic ion exchange column. Flush the column with methanol then elute desired material with 2M ammonia in methanol. Concentrate the ammonia containing eluent in vacuo to give a pale yellow solid. Dissolve the resulting solid in dichloromethane and treat with HCl (1M in ether, 5 mL). Concentrate in vacuo to obtain the title compound (81.5 mg, 0.16 mmol) 1H NMR (d6-DMSO) δ 0.82-0.73 (m, 1H), 1.33-1.23 (m, 4H), 2.88-2.80 (m, 2H), 3.36-3.31 (m, 5H), 3.81 (s, 3H), 4.23-4.19 (m, 2H), 6.73-6.63 (m, 2H), 6.87-6.77 (m, 2H), 7.15-7.09 (m, 1H), 7.41-7.36 (m, 1H), 7.62-7.54 (m, 1H), 7.87-7.77 (m, 3H), 8.09-8.05 (m, 1H), 10.58-10.45 (m, 1H).

Workup

  1. temperatureCool the mixture to room temperature
  2. concentrationconcentrate in vacuo
  3. customto give a yellow residue
  4. customCarefully quench the resulting residue with methanol and load onto an SCX acidic ion exchange column
  5. customFlush the column with methanol
  6. washthen elute desired material with 2M ammonia in methanol
  7. concentrationConcentrate the ammonia containing eluent in vacuo
  8. customto give a pale yellow solid
  9. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-b1aade89c6e04e22bd168997ddf3660b
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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