Thionyl Chloride → HCID 70982171, compound

HRID 1479187Notes

Reaction equation

HRID 1479187 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.[C:21]([O:25][C:26]([N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH:35]=2)[C:30]([NH2:45])=[N:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C.C(Cl)Cl.CO>[C:21]([O:25][C:26]([N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:39])[CH3:40])[CH:35]=2)[C:30]([NH:45][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)=[CH:16][CH:15]=2)=[N:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 7365324-(4-Methylpiperazin-1-yl)benzoic acidHCID 70982737HCID 70982737, compound

Product 1

HCID 70982171HCID 70982171, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 4-(4-methyl-piperazin-1-yl)-benzoic acid (1.64 g, 7.48 mmol) in dry THF (50 ml), under argon atmosphere, at r.t., was added thionyl chloride (1.37 ml, 18.9 mmol) and 3 drops of dry DMF. The reaction mixture was heated to 50° C. and stirred for 5 h then the volatiles were removed under reduced pressure. The residue was taken up in dry toluene (50 ml), re-evaporated and the solid residue dried under high vacuum. The resultant crude 4-(4-methyl-piperazin-1-yl)-benzoyl chloride hydrochloride was suspended in 20 ml of dry THF and treated dropwise at r.t., under argon atmosphere, with a solution of 3-amino-6-(tert-butyl-dimethyl-silanyloxy)-indazole-1-carboxylic acid tert-butyl ester (1.81 g, 4.98 mmol) in 20 ml of dry THF and 2.56 ml of DIPEA (14.96 mmol). The reaction mixture was heated to 50° C. and stirred for 22 h. The volatiles were removed under reduced pressure, the residue diluted with DCM (100 ml) and washed with a saturated solution of NaHCO3 (75 ml). The organic layer was separated, dried over sodium sulfate and evaporated to dryness. The crude residue was purified by flash chromatography over silica gel eluting with DCM/MeOH/30% NH3 95:5:0.5 affording 1.88 g (yield: 67%) of the title compound.

Workup

  1. customthe volatiles were removed under reduced pressure
  2. customre-evaporated
  3. customthe solid residue dried under high vacuum
  4. temperatureThe reaction mixture was heated to 50° C.
  5. stirringstirred for 22 h
  6. customThe volatiles were removed under reduced pressure
  7. additionthe residue diluted with DCM (100 ml)
  8. washwashed with a saturated solution of NaHCO3 (75 ml)
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-160a6cea7d264fa89df1a48063ade72f
Source dataset
uspto-grants-2016_08
Patent number
US09408850B2

Reaction notes

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