Benzenamine, 4-(4-morpholinyl)- → HCID 11634290, compound

HRID 729279Notes

Reaction equation

HRID 729279 reaction equation
[N:1]1([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:14]([N:18]1[C:22](=[O:23])[C:21](Cl)=[C:20]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=2)[S:19]1(=[O:33])=[O:32])[CH2:15][CH2:16][CH3:17]>CN(C=O)C>[CH2:14]([N:18]1[C:22](=[O:23])[C:21]([NH:11][C:10]2[CH:12]=[CH:13][C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[CH:8][CH:9]=2)=[C:20]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=2)[S:19]1(=[O:32])=[O:33])[CH2:15][CH2:16][CH3:17]

Participants

4

Reactant 2

HCID 75655Benzenamine, 4-(4-morpholinyl)-2×HCID 686616252-Butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide2×

Product 1

HCID 11634290HCID 11634290, compoundYield 184.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
140 °C

Procedure

4-Morpholin-4-ylaniline (53 mg, 0.30 mmol) was added to a solution of 2-butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (50 mg, 0.15 mmol) in dry DMF (1.0 mL) at rt and under an atmosphere of nitrogen. The reaction mixture was heated in a microwave reactor at 140° C. for 25 mins, whereafter the solvents were removed. Another portion of 4-morpholin-4-ylaniline (160 mg, 0.90 mmol) was added to a solution of 2-butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (150 mg, 0.45 mmol) in dry DMF (2.0 mL) at rt and under an atmosphere of nitrogen. The reaction mixture was heated in a microwave reactor at 140° C. for 25 mins, whereafter the solvents were removed. The obtained two mixtures were combined and purified using preparative HPLC (column ACE C8, 0.1M NH4OAc/MeCN, gradient) followed by column chromatography (Horizons Biotage, Heptane:EtOAc, 3:1, isocratic run) to give the title compound (132 mg, 62%) as a yellow solid; 1H NMR (500 MHz, CDCl3): δ 7.22 (bs, 1H), 7.13-7.19 (m, 2H), 7.06-7.11 (m, 1H), 6.93-6.96 (m, 1H), 6.65-6.69 (m, 2H), 6.55-6.60 (m, 2H), 3.82-3.86 (m, 4H), 3.75-3.80 (t, 2H), 3.04-3.08 (m, 4H), 1.83-1.91 (m, 2H), 1.44-1.52 (m, 2H), 1.01 (t, 3H); 13C NMR (125 MHz, CDCl3): δ 159.3, 149.8, 134.2, 132.6, 130.3, 129.3, 129.0, 127.9, 127.3, 126.8, 124.3, 115.6, 107.8, 66.9, 49.6, 40.5, 30.4, 20.3, 13.8; Mass Spectrum: M−H 474.

Workup

  1. customwere removed
  2. temperatureThe reaction mixture was heated in a microwave reactor at 140° C. for 25 mins, whereafter the solvents
  3. customwere removed
  4. customThe obtained two mixtures
  5. custompurified

Sources & evidence

ORD record
ord-e117932dc81941e1b4e88e3855251e96
Source dataset
uspto-grants-2009_09
Patent number
US07582629B2

Reaction notes

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