Ammonium Chloride → HCID 66600184, compound

HRID 1621557Notes

Reaction equation

HRID 1621557 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:17]([C:18]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][N:22]4[CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)=[CH:16][C:13]([CH:14]=[O:15])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.[CH3:34][Mg]Br.[Cl-].[NH4+]>C1COCC1.O>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[CH:12][C:13]([CH:14]([OH:15])[CH3:34])=[CH:16][C:17]=2[C:18]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][N:22]3[CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 59548351HCID 59548351, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 66600184HCID 66600184, compoundYield 109.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (641.5 mg, 1.440 mmol) was suspended in THF (14 mL) and the reaction was cooled in an ice bath under nitrogen. Then, methylmagnesium bromide (3.0 M solution in diethyl ether, 1.65 mL, 4.95 mmol) was added via syringe, and the reaction was allowed to warm up to room temperature. After 1 h and 45 min, the reaction was cooled in an ice bath and the reaction was treated with saturated ammonium chloride, dropwise at first as gas evolution was observed. Then, the reaction was warmed to room temperature and diluted with water (15 mL). The layers were separated, and the aqueous phase was extracted with 10:1 DCM/MeOH. The organic layer and the organic extracts were combined, concentrated, and dried under high vacuum to give 1-(6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethanol (725 mg). 1H NMR (CDCl3, 400 MHz) δ 12.52 (s, 1H), 9.81 (s, 1H), 8.43 (s, 1H), 8.36-8.19 (m, 3H), 6.83-6.77 (m, 1H), 5.88 (d, J=9.00 Hz, 1H), 5.01 (d, J=5.87 Hz, 1H), 4.21 (d, J=10.95 Hz, 1H), 3.89-3.81 (m, 1H), 2.91 (s, 3H), 2.21-1.65 (m, 6H), 1.63-1.61 (m, 3H). m/z (ESI, pos. ion) 462 (M+H)+.

Workup

  1. temperaturethe reaction was cooled in an ice bath under nitrogen
  2. temperature45 min, the reaction was cooled in an ice bath
  3. temperatureThen, the reaction was warmed to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with 10:1 DCM/MeOH
  6. concentrationconcentrated
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-1d59ab2c1664491ea7cfdda82e7b82dc
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…