(2R)-2-hydroxypropanamide → US9777017, Example 1

HRID 711931Notes

Reaction equation

HRID 711931 reaction equation
[OH:1][C@H:2]([CH3:6])[C:3](N)=O.F[B-](F)(F)F.C([O+](CC)CC)C.[O:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH:25][C:26]2[C:31]([NH2:32])=[CH:30][N:29]=[C:28]3[CH:33]=[CH:34][S:35][C:27]=23)[CH2:20]1>O1CCCC1.C(O)C>[O:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([N:25]2[C:26]3=[C:27]4[S:35][CH:34]=[CH:33][C:28]4=[N:29][CH:30]=[C:31]3[N:32]=[C:3]2[C@H:2]([OH:1])[CH3:6])[CH2:20]1

Participants

6

Reactant 3

HCID 1530236(2R)-2-hydroxypropanamideHCID 2723982Triethyloxonium tetrafluoroborateHCID 86717413N7-[(3S)-Tetrahydro-2H-pyran-3-yl]thieno[3,2-b]pyridine-6,7-diamine

Product 1

HCID 73776195US9777017, Example 1Yield 65%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2R)-2-hydroxypropanamide (from Aldrich, 5.4 mg, 0.060 mmol) and triethyloxonium tetrafluoroborate (12 mg, 0.062 mmol) in tetrahydrofuran (0.1 mL) became a solution after stirred for 15 min. After another 45 min, this solution was added to a mixture of N7-[(3S)-tetrahydro-2H-pyran-3-yl]thieno[3,2-b]pyridine-6,7-diamine (7.5 mg, 0.030 mmol) in ethanol (0.24 mL) and the resultant mixture was heated at reflux for 2 h. The crude mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (5.9 mg, 65%). LCMS calculated for C15H18N3O2S (M+H)+: m/z=304.1. Found: 304.0.

Workup

  1. waitAfter another 45 min
  2. temperatureat reflux for 2 h
  3. customThe crude mixture was purified on RP-HPLC (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-2ba9b244872e450b9f7f232e32d722ae
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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