Sodium Iodide → HCID 59426223, compound

HRID 907154Notes

Reaction equation

HRID 907154 reaction equation
[O:1]=[S:2]1(=[O:27])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:25][CH3:26])[C:15]3[C:20]([C:21]=2[C:22]#[N:23])=[CH:19][CH:18]=[C:17]([OH:24])[CH:16]=3)=[CH:9][CH:8]=1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+].Cl.Cl[CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1>C(C(C)=O)C.O.CN(C=O)C>[O:27]=[S:2]1(=[O:1])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]([CH2:25][CH3:26])[C:15]3[C:20]([C:21]=2[C:22]#[N:23])=[CH:19][CH:18]=[C:17]([O:24][CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH:16]=3)=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium Carbonate2×HCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)2×HCID 59425169HCID 59425169, compound

Product 1

HCID 59426223HCID 59426223, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-[4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl]-1-ethyl-6-hydroxy-1H-indole-3-carbonitrile, prepared in example 1AT above (70 mg, 0.25 mmol), K2CO3 (75 mg, 0.51 mmol), sodium iodide (27 mg, 0.18 mmol), 4-(2-chloroethyl) morpholine hydrochloride (42 mg, 0.25 mmol) in methyl ethyl ketone (3 mL) was heated in a sealed tube at 100° C. After 13 hours, DMF (3 mL) was added and the reaction was heated for an additional 6 h. After this time, an additional 42 mg of 4-(2-chloroethyl) morpholine hydrochloride and 135 mg of K2CO3 was added and the reaction was heated for an additional 6 h to complete the reaction. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic phases were washed with water (2×) and saturated NaCl and dried and concentrated. Pure 2-[4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-phenyl]-1-ethyl-6-(2-morpholin-4-yl-ethoxy)-1H-indole-3-carbonitrile was obtained by flash chromatography (MeOH/CH2Cl2, 0-6%) to give 29 mg (34%) of a tan solid.

Workup

  1. temperaturethe reaction was heated for an additional 6 h
  2. temperaturethe reaction was heated for an additional 6 h
  3. customthe reaction
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organic phases were washed with water (2×) and saturated NaCl
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6e216ee38f5946ee8932a09dcde4ed78
Source dataset
uspto-grants-2011_09
Patent number
US08013006B2

Reaction notes

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