Acetone → RAS-2410 hydrochloride

HRID 1627752Notes

Reaction equation

HRID 1627752 reaction equation
[NH2:1][OH:2].C1COCC1.Cl.[CH3:9][N:10]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([S:19]([N:22]2[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([Cl:31])=[O:30])=[CH:23]2)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[CH3:11].CC(C)=O>C(#N)C>[ClH:31].[CH3:9][N:10]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([S:19]([N:22]2[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([NH:1][OH:2])=[O:30])=[CH:23]2)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[CH3:11]

Participants

6

Reactant 4

HCID 180AcetoneHCID 787HydroxylamineHCID 8028TetrahydrofuranHCID 86653102HCID 86653102, compound

Product 1

HCID 16662815RAS-2410 hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
9 °C

Procedure

A second reaction vessel was charged with aqueous hydroxylamine (50%, 42.8 kg, 647 mol) and THF (40.0 L). The above prepared solution of (E)-3-[1-(4-dimethylaminomethyl-benzenesulfonyl)-1H-pyrrol-3-yl]-acryloyl chloride hydrochloride was added at 18-30° C. over a period of 2-4 h. After stirring for 20-40 min, acetone (47.6 L, 647 mmol) was added at 17-25° C. within 45-90 min. The reaction mixture was stirred for 30 min and acetonitrile (570.0 L) was added over a period of 1-2 h. The suspension was stirred at 17-25° C. for at least 4 h, cooled to 5-13° C. and stirred for 1-2 h. The solid was centrifuged and was used without further drying in the subsequent free basing step.

Workup

  1. additionwas added at 18-30° C. over a period of 2-4 h
  2. stirringThe reaction mixture was stirred for 30 min
  3. stirringThe suspension was stirred at 17-25° C. for at least 4 h
  4. stirringstirred for 1-2 h
  5. customwithout further drying in the subsequent free basing step

Sources & evidence

ORD record
ord-8df2d2d03e5e467abf8ee82ff424def8
Source dataset
uspto-grants-2014_07
Patent number
US08785659B2

Reaction notes

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