Tetrahydrofuran → HCID 71283593, compound

HRID 1752410Notes

Reaction equation

HRID 1752410 reaction equation
[CH:1]12[O:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[N:10]=[C:9]([C:27]([NH2:29])=[O:28])[CH:8]=1)[CH2:2]2.C1C[O:33]CC1>O>[OH:6][CH:1]1[CH:5]([OH:33])[CH2:4][N:3]([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[N:10]=[C:9]([C:27]([NH2:29])=[O:28])[CH:8]=2)[CH2:2]1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 89422459HCID 89422459, compound

Product 1

HCID 71283593HCID 71283593, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of the 6-(6-oxa-3-azabicyclo[3.1.0]hexan-3-yl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide (0.050 g, 0.13 mmol) in THF (5 mL) and water (1 mL) was added a 60% HClO4 solution (0.1 mL). After stirring overnight, the reaction was heated at 50° C. for 2 days. After the reaction cooled it was quenched with solid NaHCO3 and evaporated in vacuo. The residue was chromatographed over silica gel with 50-100% acetone in hexanes. The product fractions were evaporated and the resulting residue dissolved in 1 mL acetonitrile with warming. Upon cooling a solid formed. The solid was filtered and rinsed once with 1 mL acetonitrile. The remaining solid was suspended in 1 mL warm acetonitrile, filtered and air-dried to give 6-(3,4-dihydroxypyrrolidin-1-yl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as a fine crystalline powder (0.009 g, 0.02 mmol, 17%). 1H NMR (400 MHz, DMSO-d6): 8.55 (2H, d, J=8.8 Hz), 8.34 (1H, d, J=2.4 Hz), 7.88 (1H, d, J=2.4 Hz), 7.31-7.24 (2H, m), 7.19-7.13 (2H, m), 7.05 (2H, d, J=9.0 Hz), 6.90 (1H, s), 5.29 (1H, d, J=3.7 Hz), 5.22 (1H, d, J=3.3 Hz), 4.14-4.10 (1H, m), 4.09-4.05 (1H, m), 3.76-3.63 (3H, m), 3.35-3.30 (1H, m). LC/MS: m/z=411.1 [M+H]+.

Workup

  1. temperatureAfter the reaction cooled it
  2. customwas quenched with solid NaHCO3
  3. customevaporated in vacuo
  4. customThe residue was chromatographed over silica gel with 50-100% acetone in hexanes
  5. customThe product fractions were evaporated
  6. dissolutionthe resulting residue dissolved in 1 mL acetonitrile
  7. temperaturewith warming
  8. temperatureUpon cooling a solid
  9. customformed
  10. filtrationThe solid was filtered
  11. washrinsed once with 1 mL acetonitrile
  12. temperaturewarm acetonitrile
  13. filtrationfiltered
  14. customair-dried

Sources & evidence

ORD record
ord-89e6fdbf04f544dca79fed389f062cbe
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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