Diisopropylethylamine → HCID 178504692, compound

HRID 1409767Notes

Reaction equation

HRID 1409767 reaction equation
Cl.[NH2:2][OH:3].[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]([CH:31]2[CH2:33][CH2:32]2)[C:13]([C:15]2[CH:16]=[N:17][C:18]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=3)=[N:19][CH:20]=2)=[O:14])[CH2:8][CH2:7]1)#[N:5].C(N(C(C)C)C(C)C)C>C(O)C>[CH:31]1([N:12]([CH:9]2[CH2:10][CH2:11][N:6]([C:4](=[NH:5])[NH:2][OH:3])[CH2:7][CH2:8]2)[C:13]([C:15]2[CH:20]=[N:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=3)=[N:17][CH:16]=2)=[O:14])[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochloride2×HCID 86686171HCID 86686171, compound2×

Product 1

HCID 178504692HCID 178504692, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Hydroxylamine hydrochloride (21 mg) is added to 2-(4-methanesulfonyl-phenyl)-pyrimidine-5-carboxylic acid (1-cyano-piperidin-4-yl)-cyclopropyl-amide (130 mg, Intermediate 22) and ethyldiisopropylamine (634) in ethanol (30 mL) and the mixture is refluxed for 4 h. Another 10 mg hydroxylamine hydrochloride is added and the mixture is refluxed for 1 h and stirred at room temperature for 12 h. The solvent is removed in vacuo and the residue is purified by preparative HPLC (MeOH/H2O/TFA) to yield 2-(4-methanesulfonyl-phenyl)-pyrimidine-5-carboxylic acid cyclopropyl-[1-(N-hydroxycarbamimidoyl)-piperidin-4-yl]-amide as an intermediate. Subsequently 50 mg of the aforementioned intermediate are added to tetrahydrofuran (10 mL) followed by ethyldiisopropylamine (28 μL) and cyclopropanecarbonyl chloride (10 μL). The mixture is stirred at room temperature for 3 h. Acetonitrile is added and the mixture is refluxed for 12 h. After removal of the solvents the residue is purified by HPLC (MeOH/H2O/ammonia) to yield the desired product. LC (method 16): tR=1.17 min; Mass spectrum (ESI+): m/z=509 [M+H]+.

Workup

  1. temperaturethe mixture is refluxed for 4 h
  2. temperaturethe mixture is refluxed for 1 h
  3. customThe solvent is removed in vacuo
  4. customthe residue is purified by preparative HPLC (MeOH/H2O/TFA)

Sources & evidence

ORD record
ord-6e3ab7c468a84cbe9fdc77915e72bb1c
Source dataset
uspto-grants-2014_12
Patent number
US08921398B2

Reaction notes

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