4-Methylmorpholine → HCID 178485804, compound

HRID 1672474Notes

Reaction equation

HRID 1672474 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[C:12]([O:20][CH2:21][C:22](O)=[O:23])[C:13]([CH3:19])=[CH:14][CH:15]=3)[N:10]=2)[CH2:4][CH2:3]1.[CH3:25][N:26]1CCOCC1.Cl.CN.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CO.C1COCC1.CN(C=O)C>[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[C:12]([O:20][CH2:21][C:22]([NH:26][CH3:25])=[O:23])[C:13]([CH3:19])=[CH:14][CH:15]=3)[N:10]=2)[CH2:4][CH2:3]1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 178422923HCID 178422923, compound

Product 1

HCID 178485804HCID 178485804, compoundYield 64.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of ({2-[(trans-4-hydroxycyclohexyl)amino]-7-methylquinazolin-8-yl}oxy)acetic acid (1.8 g, 5.4 mmol) in the mixed solvents of DMF (36 mL) and THF (36 mL) were added NMM (2.3 g, 21 mmol), methylamine hydrochloride (0.44 g, 6.5 mmol), HOBt (1.47 g, 11 mmol) and EDCl (2.08 g, 11 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight. TLC(CH2Cl2/MeOH=2:1) indicated the reaction was complete. The mixture was concentrated in vacuo. The residue was taken up with CH2Cl2 (100 mL), washed with 5% aq. Na2CO3 (30 mL×2) and brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to give the crude product. The crude product was purified by silica gel chromatography (CH2Cl2˜CH2Cl2/MeOH=100:1 to CH2Cl2/MeOH=80:1) to give the title compound (1.2 g, 63.2%) as a light yellow solid. 1H NMR (MeOD) δ (ppm) 8.90 (1H, s), 7.39 (1H, d), 7.40 (1H, m), 4.689 (2H, s), 3.84 (1H, m), 3.67 (1H, m), 2.94 (3H, s), 2.40 (3H, s), 2 54 (4H, m), 1.39 (4H, m).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. washwashed with 5% aq. Na2CO3 (30 mL×2) and brine
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThe crude product was purified by silica gel chromatography (CH2Cl2˜CH2Cl2/MeOH=100:1 to CH2Cl2/MeOH=80:1)

Sources & evidence

ORD record
ord-d91e5e911afd4cfe8d81576dc12affdd
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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