Methanol → HCID 86669032, compound

HRID 2366322Notes

Reaction equation

HRID 2366322 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:27])[C:9]=1[C:10]1[S:11][C:12]2[C:13]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[N:23]=[CH:22][N:21]=3)=[N:14][CH:15]=[CH:16][C:17]=2[N:18]=1)[C:5]#[N:6].[CH3:28][O-:29].[Na+].[Cl-].[NH4+:32].C[OH:34]>>[CH:28]([OH:34])=[O:29].[CH:28]([OH:34])=[O:29].[CH3:26][C:24]1[N:23]=[CH:22][N:21]=[C:20]([NH:19][C:13]2[C:12]3[S:11][C:10]([C:9]4[C:8]([Cl:27])=[CH:7][C:4]([C:5]([NH2:32])=[NH:6])=[CH:3][C:2]=4[Cl:1])=[N:18][C:17]=3[CH:16]=[CH:15][N:14]=2)[CH:25]=1

Participants

5

Reactant 4

HCID 887Methanol3×HCID 25517Ammonium Chloride2×HCID 10942334Sodium Methoxide2×HCID 56952206HCID 56952206, compound

Product 1

HCID 86669032HCID 86669032, compoundYield 10%

Procedure

To a solution of 3,5-dichloro-4-[4-(6-methylpyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]benzonitrile (54 mg, 0.12 mmol) in MeOH (3 mL) was added a solution of sodium methoxide in methanol (0.054 mL, 0.24 mmol) and the reaction mixture was stirred at room temperature for 48 hours. After this time, an additional portion of sodium methoxide in methanol (0.0082 mL, 0.14 mmol) was added, stirred for 1 hour and then ammonium chloride (7.0 mg, 7.1 mmol) was added and the resultant mixture was heated at reflux overnight. After cooling to room temperature, additional ammonium chloride (11.4 mg, 0.21 mmol) was added and heated at reflux for a further 5 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resultant residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 minute gradient 5-50%, 0.1% HCO2H in CH3CN/H2O) to afford the title compound (5.6 mg, 10% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.75 (br s, 1H), 9.60 (s, 2H), 9.34 (s, 2H), 8.61 (s, 1H), 8.42 (d, J=5.5 Hz, 1H), 8.14 (s, 2H), 7.82 (d, J=5.3 Hz, 1H), 7.54 (s, 1H), 2.41 (s, 3H). LCMS (Method C): RT=2.06 min, m/z: 412 [M+H+].

Workup

  1. stirringstirred for 1 hour
  2. temperatureat reflux overnight
  3. temperatureAfter cooling to room temperature
  4. temperatureheated
  5. temperatureat reflux for a further 5 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. concentrationconcentrated under reduced pressure
  8. customThe resultant residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 25 minute gradient 5-50%, 0.1% HCO2H in CH3CN/H2O)

Sources & evidence

ORD record
ord-cf9827557477400a92338b448a544546
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

Loading…