Triphenylphosphine → US10188653, Example 17

HRID 59929Notes

Reaction equation

HRID 59929 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OCCOC)=O)=N\C(OCCOC)=O.[CH2:36]([O:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[OH:47])[C:42]#[N:43])[CH3:37].[CH2:48]([NH:50][C:51]([C:53]1[CH:54]=[N:55][C:56]([N:59]2[CH2:64][CH2:63][CH2:62][C@H:61](O)[CH2:60]2)=[N:57][CH:58]=1)=[O:52])[CH3:49]>C1COCC1.CCOCC>[C:42]([C:41]1[CH:44]=[CH:45][C:46]([O:47][C@@H:61]2[CH2:62][CH2:63][CH2:64][N:59]([C:56]3[N:57]=[CH:58][C:53]([C:51]([NH:50][CH2:48][CH3:49])=[O:52])=[CH:54][N:55]=3)[CH2:60]2)=[C:39]([O:38][CH2:36][CH3:37])[CH:40]=1)#[N:43]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 38006593-Ethoxy-4-hydroxybenzonitrileHCID 22836032Bis(2-methoxyethyl) diazene-1,2-dicarboxylateHCID 118366212(S)-N-ethyl-2-(3-hydroxypiperidin-1-yl)pyrimidine-5-carboxamide

Product 1

HCID 118366240US10188653, Example 17

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
22.5 °C

Procedure

A solution of triphenylphosphine (65 mg, 0.25 mmol) in THF (1 mL) and a solution of bis(2-methoxyethyl) (E)-diazene-1,2-dicarboxylate (56 mg, 0.24 mmol) in THF (1 mL) were added sequentially to a solution of 3-ethoxy-4-hydroxybenzonitrile (26 mg, 0.16 mmol) and (S)—N-ethyl-2-(3-hydroxypiperidin-1-yl)pyrimidine-5-carboxamide (40 mg, 0.16 mmol) in THF (2 mL) at 20-25° C. The reaction mixture was stirred at 20-25° C. for 16 hours. The mixture was diluted with ether (30 mL), and was washed sequentially with aqueous 1N NaOH solution (1 mL) and brine (1 mL). The organic phase was dried over MgSO4, filtered, and concentrated to provide a crude residue, which was purified via preparative HPLC to afford (R)-2-(3-(4-cyano-2-ethoxyphenoxy)piperidin-1-yl)-N-ethylpyrimidine-5-carboxamide. HPLC: Waters XBridge dC18 4.6×50 mm, 5 μm, 95% water/5% acetonitrile linear to 5% water/95% acetonitrile over 4.0 min, 0.03% NH4OH modifier, 2 mL/min; retention time 2.60 min. MS (ES+) 396.1 (M+H).

Workup

  1. washwas washed sequentially with aqueous 1N NaOH solution (1 mL) and brine (1 mL)
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a crude residue, which
  6. customwas purified via preparative HPLC

Sources & evidence

ORD record
ord-82915688afed4baea3a2d6137ca8886a
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Reaction notes

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