Potassium Carbonate → HCID 54671131, compound

HRID 869030Notes

Reaction equation

HRID 869030 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[NH2:11][C:12]1[C:13]([C:30]#[C:31][C:32]2[CH:33]=[C:34]([OH:38])[CH:35]=[CH:36][CH:37]=2)=[N:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH:27]([CH3:29])[CH3:28])(=[O:26])=[O:25])=[CH:20][CH:19]=2)=[CH:16][N:17]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:27]([S:24]([C:21]1[CH:20]=[CH:19][C:18]([C:15]2[N:14]=[C:13]([C:30]#[C:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH2:3][CH2:4][N:5]4[CH2:10][CH2:9][O:8][CH2:7][CH2:6]4)[CH:33]=3)[C:12]([NH2:11])=[N:17][CH:16]=2)=[CH:23][CH:22]=1)(=[O:25])=[O:26])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 54670657HCID 54670657, compound

Product 1

HCID 54671131HCID 54671131, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

4-(2-Chloroethyl)morpholine hydrochloride (31.93 mg, 0.1716 mmol) was added to a stirred solution of 3-[2-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]ethynyl]phenol (45 mg, 0.1144 mmol) and K2CO3 (39.53 mg, 0.2860 mmol) in DMF (1 mL) and the reaction mixture warmed to 65° C. for 16 hours. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3 and stirred for 5 minutes. The layers were separated by filtration through a phase separation cartridge and the aqueous layer retained was washed with DCM (×2). The combined organic extracts were passed through a 5 g SCX-2 cartridge and washed with MeOH. The product was eluted by washing the cartridge with 2M NH3 in MeOH. The solvent was removed in vacuo and the material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the mono-TFA salt of the title compound as a yellow solid (29 mg, 41% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.09 (d, 6H), 3.22-3.25 (m, 2H), 3.41-3.74 (m, 7H), 4.01 (d, 2H), 4.43 (s, 2H), 6.98 (s, 2H), 7.14 (d, 1H), 7.41-7.48 (m, 3H), 7.92 (d, 2H), 8.23 (d, 2H), 8.78 (s, 1H) and 9.88 (s, 1H) ppm; (ES+) 507.3.

Workup

  1. customThe reaction mixture was partitioned between DCM and saturated aqueous NaHCO3
  2. customThe layers were separated by filtration through a phase separation cartridge
  3. washthe aqueous layer retained was washed with DCM (×2)
  4. washwashed with MeOH
  5. washThe product was eluted
  6. washby washing the cartridge with 2M NH3 in MeOH
  7. customThe solvent was removed in vacuo
  8. customthe material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-0722bf86405b4bb686ffe8a332c45742
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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