Potassium Carbonate → HCID 86714545, compound

HRID 409165Notes

Reaction equation

HRID 409165 reaction equation
[NH2:1][C:2]([CH3:40])([CH3:39])[CH:3]=[C:4]([C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[CH2:14][N:15]1[C:19]2=[N:20][CH:21]=[N:22][C:23]([NH2:24])=[C:18]2[C:17]([C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:27][C:26]=2[F:38])=[N:16]1)=[O:8])[C:5]#[N:6].C(=O)([O-])[O-].[K+].[K+].Br[CH2:48][CH2:49][O:50][CH3:51]>CC#N>[NH2:24][C:23]1[N:22]=[CH:21][N:20]=[C:19]2[N:15]([CH2:14][C@@H:10]3[CH2:11][CH2:12][CH2:13][N:9]3[C:7]([C:4](=[CH:3][C:2]([NH:1][CH2:48][CH2:49][O:50][CH3:51])([CH3:40])[CH3:39])[C:5]#[N:6])=[O:8])[N:16]=[C:17]([C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:27][C:26]=3[F:38])[C:18]=12

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 71015231HCID 71015231, compound

Product 1

HCID 86714545HCID 86714545, compoundYield 3.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 4-amino-2-((S)-2-((4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidine-1-carbonyl)-4-methylpent-2-enenitrile (210 mg, 0.39 mmol, 1.0 equiv), KI (130 mg, 0.78 mmol, 2.0 equiv) and potassium carbonate (166 mg, 1.17 mmol, 3.0 equiv) in CH3CN (15 mL) was added 1-bromo-2-methoxyethane (160 mg, 1.17 mmol, 3.0 equiv). The resulting suspension was stirred at 50° C. overnight. The solvent was removed under reduced pressure and then water (20 mL) was added to the residue. The resulting mixture was extracted with ethyl acetate (30 mL*3). The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated. The residue was purified on Prep-HPLC. Conditions: (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, WATER WITH 0.5% NH4OH and CH3CN (40% CH3CN up to 100% in 20 min); Detector, 254 nm. This resulted in 8.7 mg (3.7%) of the title compound as an off-white solid. MS (ESI, pos. ion) m/z: 599 (M+1) H-NMR (400 MHz, CDCl3, ppm): 8.38 (s, 1H), 7.54 (t, J=8.4, 7.2 Hz, 1H), 7.45 (t, J=7.6, 8.0 Hz, 2H), 7.28-7.25 (m, 1H), 7.13 (d, J=8.0 Hz, 2H), 6.95 (dd, J=8.4, 2.0 Hz, 1H), 6.87 (dd, J=11.2, 2.4 Hz, 1H), 6.77 (s, 1H), 5.42 (brs, 2H), 4.93-4.90 (m, 1H), 4.83-4.82 (m, 1H), 4.70-4.65 (m, 1H), 3.67-3.65 (m, 5H), 3.36 (s, 3H), 3.36-3.31 (m, 1H), 2.20-2.89 (m, 3H), 1.88-1.71 (m, 1H), 1.61-1.51 (m, 4H), 1.35 (s, 3H), 1.33 (s, 3H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionwater (20 mL) was added to the residue
  3. extractionThe resulting mixture was extracted with ethyl acetate (30 mL*3)
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified on Prep-HPLC
  8. waitmobile phase, WATER WITH 0.5% NH4OH and CH3CN (40% CH3CN up to 100% in 20 min)

Sources & evidence

ORD record
ord-d4569dab294449b7b15b3ee0c64fecdd
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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