Triethylamine → (2S)-1-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)propan-2-ol

HRID 1052262Notes

Reaction equation

HRID 1052262 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][NH:25][CH:26]=4)[N:19](S(C4C=CC=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[CH3:36][C@H:37]1[CH2:39][O:38]1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:26]=[N:25][N:24]([CH2:36][C@@H:37]([OH:38])[CH3:39])[CH:23]=4)[NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 146262(2S)-2-MethyloxiraneHCID 89963624HCID 89963624, compound

Product 1

HCID 73054517(2S)-1-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)propan-2-olYield 15.2%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-6-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine (from Example 35, Step 1, 30.0 mg, 0.0613 mmol) and (S)-(−)-methyloxirane (8.56 μL, 0.122 mmol) in isopropyl alcohol (2 mL)/N,N-dimethylformamide (0.5 mL), triethylamine (17.1 μL, 0.122 mmol) was added at ambient temperature. The reaction mixture was then warmed up to 90° C. After 2 hours, the volatiles were removed and the residue was dissolved in methanol (2 mL). Potassium carbonate (16.9 mg, 0.122 mmol) was added and the reaction mixture was warmed up to 60° C. After 30 minutes, the crude mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (3.8 mg) as its TFA salt. LCMS calculated for C22H26N5O3 (M+H)+: m/z=408.2. Found: 408.2.

Workup

  1. customthe volatiles were removed
  2. dissolutionthe residue was dissolved in methanol (2 mL)
  3. temperaturethe reaction mixture was warmed up to 60° C
  4. waitAfter 30 minutes
  5. customthe crude mixture was purified on RP-HPLC (XBridge C18 column
  6. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-669cd72ac26b46ec8a22f2afd35cae0e
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

Loading…