Triethylamine → 4-bromo-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide

HRID 1497332Notes

Reaction equation

HRID 1497332 reaction equation
[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([OH:14])=O)[CH:3]=1.Cl.[NH2:16][C@H:17]1[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]1[OH:23].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH:16][C@H:17]2[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]2[OH:23])=[O:14])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 155308124-Bromoquinoline-2-carboxylic acidHCID 67324376(3R,4S)-4-aminooxan-3-ol hydrochloride

Product 1

HCID 602099134-bromo-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-bromoquinoline-2-carboxylic acid (A3) (0.5 g, 2.0 mmol) in 10 mL CH2Cl2 was added (3R,4S)-4-aminotetrahydro-2H-pyran-3-ol hydrogen chloride (0.37 g, 2.4 mmol), BOP reagent (1.1 g, 2.6 mmol), and triethylamine (0.83 mL, 6.0 mmol). The reaction was stirred at room temperature for 4.5 h, diluted with CH2Cl2, washed twice with water, dried over sodium sulfate, filtered, and concentrated. The resultant residue was subjected to silica gel chromatography eluting with 30-100% ethyl acetate in hexanes to afford 4-bromo-N-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]quinoline-2-carboxamide (O1) that gave a mass ion (ES+) of 353.2 (81Br) for M+H+.

Workup

  1. washwashed twice with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washeluting with 30-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d73b1c9232d7494ab2df766c03317aea
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

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