Water → 4-(morpholin-4-yl)-5-[3-(1,2,4-oxadiazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 1750302Notes

Reaction equation

HRID 1750302 reaction equation
[CH:1](OCC)(OCC)OCC.B(F)(F)F.CCOCC.[OH:20][N:21]=[C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[C:38]3[C:37]([N:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)=[N:36][CH:35]=[N:34][C:33]=3[N:32](COCC[Si](C)(C)C)[CH:31]=2)[CH:25]=1)[NH2:23].O>O1CCCC1>[N:39]1([C:37]2[C:38]3[C:30]([C:26]4[CH:27]=[CH:28][CH:29]=[C:24]([C:22]5[N:23]=[CH:1][O:20][N:21]=5)[CH:25]=4)=[CH:31][NH:32][C:33]=3[N:34]=[CH:35][N:36]=2)[CH2:40][CH2:41][O:42][CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 962WaterHCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 86706972HCID 86706972, compound

Product 1

HCID 867069734-(morpholin-4-yl)-5-[3-(1,2,4-oxadiazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

Triethyl orthoformate (760 mg, 5.1 mol) and boron trifluoride diethyl etherate (370 mg, 2.6 mol) were added to a 0° C. solution of N′-hydroxy-3-[4-(morpholin-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzenecarboximidamide (C35) (600 mg, 1.3 mmol) in tetrahydrofuran (25 mL). The reaction mixture was heated at 40° C. for 18 hours, then poured into water (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated. Purification via preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 30% to 50% B) provided the product as a yellow solid. Yield: 62 mg, 0.18 mmol, 14%. LCMS m/z 349.0 [M+H+]. 1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.40 (s, 1H), 8.24 (br s, 1H), 7.98 (br d, J=7.5 Hz, 1H), 7.82 (br d, J=7.3 Hz, 1H), 7.63-7.70 (m, 2H), 3.39-3.45 (m, 4H), 3.13-3.20 (m, 4H).

Workup

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via preparative reversed phase high-performance liquid chromatography (Column: Phenomenex Gemini C18, 8 μm; Mobile phase A: aqueous ammonia, pH 10; Mobile phase B: acetonitrile; Gradient: 30% to 50% B)

Sources & evidence

ORD record
ord-39a8e98ef65f4abab14702b2ab48e2fa
Source dataset
uspto-grants-2015_10
Patent number
US09156845B2

Reaction notes

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