Ethylene Glycol → HCID 68813138, compound

HRID 2105219Notes

Reaction equation

HRID 2105219 reaction equation
[H-].[Na+].Cl[C:4]1[N:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][CH:11]2[C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[CH:16]=2)[N:7]=[C:6]([NH:26][C:27]2[CH:31]=[C:30]([CH:32]3[CH2:34][CH2:33]3)[NH:29][N:28]=2)[CH:5]=1.[CH2:35]([OH:38])[CH2:36][OH:37]>>[OH:37][CH2:36][CH2:35][O:38][C:4]1[N:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][CH:11]2[C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[CH:16]=2)[N:7]=[C:6]([NH:26][C:27]2[CH:31]=[C:30]([CH:32]3[CH2:34][CH2:33]3)[NH:29][N:28]=2)[CH:5]=1

Participants

4

Reactant 3

HCID 174Ethylene GlycolHCID 24758Sodium hydrideHCID 86610856HCID 86610856, compound

Product 1

HCID 68813138HCID 68813138, compoundYield 14%

Conditions

Temperature
150 °C

Procedure

Sodium hydride (60% dispersion in oil, 71 mg, 1.78 mmol) was added to ethylene glycol (4 ml) and the mixture stirred for 5 minutes. S-6-Chloro-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidine (Example 143) (160 mg, 0.35 mmol) was added and the mixture heated at 150° C. in a sealed vessel under microwave irradiation for 45 minutes. The crude mixture was purified by reverse phase HPLC using a C18 column eluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2). The product containing fractions were poured onto a 20 g SCX-2 column, eluting with methanol then with 2N methanolic ammonia to elute the product. The solvent was removed by evaporation to give the title compound (23 mg, 14%) as a pale yellow powder.

Workup

  1. customThe crude mixture was purified by reverse phase HPLC
  2. washeluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2)
  3. additionThe product containing fractions
  4. additionwere poured onto a 20 g SCX-2 column
  5. washeluting with methanol
  6. washwith 2N methanolic ammonia to elute the product
  7. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-50c08b18110a4551b3bfbc2d1c806d77
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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