1,2-Dichloroethane → 4-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamide

HRID 2169559Notes

Reaction equation

HRID 2169559 reaction equation
[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([OH:17])=O)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C@H:39]([NH2:41])[CH3:40])=[CH:35][CH:34]=1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH:10]2[C:15]([NH:41][C@@H:39]([C:36]2[CH:37]=[CH:38][C:33]([Cl:32])=[CH:34][CH:35]=2)[CH3:40])=[O:17])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 1715226(1R)-1-(4-chlorophenyl)ethan-1-amineHCID 86670107HCID 86670107, compound

Product 1

HCID 866701084-(5-bromo-2-chloropyrimidin-4-yl)-N-((R)-1-(4-chlorophenyl)ethyl)morpholine-3-carboxamideYield 40.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(5-Bromo-2-chloropyrimidin-4-yl)morpholine-3-carboxylic acid (PREPARATION x30, 1 g, 3.10 mmol), EDC (0.892 g, 4.65 mmol), HOBt (0.712 g, 4.65 mmol), (R)-1-(4-chlorophenyl)ethanamine (0.724 g, 4.65 mmol) and triethylamine (1.296 mL, 9.30 mmol) were dissolved in DMF (15 mL). The resulting brown solution was stirred at room temperature for 18 hours and was subsequently diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give a crude product which was loaded onto an ISCO® silica gel cartridge (40 g) and eluted using an ethyl acetatehexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow foam (574 mg, 40%). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (dd, J=7.07, 4.29 Hz, 3 H), 3.55 (d, J=6.32 Hz, 2 H), 3.68-3.79 (m, 1 H), 3.84-3.91 (m, 1 H), 4.22-4.39 (m, 2 H), 4.86 (m, 1 H), 4.89-5.03 (m, 1 H), 7.31-7.41 (m, 4 H), 8.45 (d, J=10.61 Hz, 2 H).

Workup

  1. washwashed with aqueous saturated NH4Cl (3×25 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude product which
  6. washeluted
  7. customThe product was collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0ad7e345af284774a713990a4e67cd4d
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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