4-Methylmorpholine → N-[(1R,2S)-2-hydroxy-1-phenylpropyl]-3-[(methylsulfonyl)amino]-2-phenylquinolin-4-carboxamide

HRID 655914Notes

Reaction equation

HRID 655914 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[C:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:8][C:9]2[C:14]([C:15]=1[C:16]([OH:18])=O)=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:4])=[O:3].C1C=C2N=NN(O)C2=CC=1.O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.[NH2:55][C@H:56]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C@@H:57]([OH:59])[CH3:58]>C(Cl)Cl>[OH:59][C@@H:57]([CH3:58])[C@H:56]([NH:55][C:16]([C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:6]=1[NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[O:18])[C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1

Participants

7

Reactant 5

HCID 79724-Methylmorpholine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 578935713-[(Methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acidHCID 68704476(1R,2S)-1-amino-1-phenylpropan-2-ol hydrochloride

Product 1

HCID 23649332N-[(1R,2S)-2-hydroxy-1-phenylpropyl]-3-[(methylsulfonyl)amino]-2-phenylquinolin-4-carboxamideYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-methanesulfonylamino-2-phenyl-4-carboxylic acid (1c) (250 mg, 0.73 mmol), HOBt hydrate (148 mg, 1.1 mmol), 4-methylmorpholine (160 μL, 1.46 mmol) in methylene chloride (15 mL) was added EDCI (210 mg, 1.1 mmol) at RT under N2. A mixture of (1R,2S)-1-amino-1-phenylpropan-2-ol hydrochloride and 4-methylmorpholine (193 μL, 1.75 mmol), in methylene chloride (5 mL) was added and the reaction mixture was stirred at RT for 16 h. Solution is partitioned against water and twice extracted with methylene chloride. The combined organic extracts are washed with brine, dried over magnesium sulfate and then concentrated in vacuo with added silica. The compound is subsequently eluted off the silica and chromatographed, eluting with 15-30% ethyl acetate/dichloromethane to give the title compound (167 mg, 48%). 1H NMR (500.333 MHz, CDCl3) δ 1.10 (d, J=6.6 Hz, 3H), 2.23 (s, 3H), 2.69 (d′, J=6.7 Hz, 1H), 4.44-4.47 (m, 1H), 5.35 (dd, J=8.4, 3.3 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.39 (dd, J=6.9, 6.9 Hz, 2H), 7.44 (d, J=7.5 Hz, 2H), 7.47-7.55 (m, 4H), 7.71-7.78 (m, 4H), 8.16 (d, J=8.4 Hz, 1H) MS APCI, m/z=476.1 (M+1). LCMS: 1.86 min.

Workup

  1. customSolution is partitioned against water
  2. extractiontwice extracted with methylene chloride
  3. washThe combined organic extracts are washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo with added silica
  6. washThe compound is subsequently eluted off the silica
  7. customchromatographed
  8. washeluting with 15-30% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-b657c8ac0cc94255b06e885fda2f05ca
Source dataset
uspto-grants-2011_12
Patent number
US08071621B2

Reaction notes

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