Trichloroacetyl isocyanate → (S)-(4-(4-(3-methyl-4-(piperidine-1-carbonyl)piperazin-1-yl)pyrido[3,4-d]pyridazin-1-yl)phenyl)methyl carbamate

HRID 1514370Notes

Reaction equation

HRID 1514370 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[N:13][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:22])[C@@H:17]([CH3:29])[CH2:16]3)=[C:11]3[CH:30]=[N:31][CH:32]=[CH:33][C:10]=23)=[CH:5][CH:4]=1.ClC(Cl)(Cl)[C:36]([N:38]=C=O)=[O:37]>C(Cl)(Cl)Cl>[C:36](=[O:37])([O:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[N:13][C:12]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([N:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)=[O:22])[C@@H:17]([CH3:29])[CH2:16]3)=[C:11]3[CH:30]=[N:31][CH:32]=[CH:33][C:10]=23)=[CH:5][CH:4]=1)[NH2:38]

Participants

4

Reactant 2

HCID 76400Trichloroacetyl isocyanateHCID 25226572(S)-(4-(1-(4-(hydroxymethyl)phenyl)pyrido[3,4-d]pyridazin-4-yl)-2-methylpiperazin-1-yl)(piperidin-1-yl)methanone

Product 1

HCID 57657609(S)-(4-(4-(3-methyl-4-(piperidine-1-carbonyl)piperazin-1-yl)pyrido[3,4-d]pyridazin-1-yl)phenyl)methyl carbamate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (S)-(4-(1-(4-(hydroxymethyl)phenyl)pyrido[3,4-d]pyridazin-4-yl)-2-methylpiperazin-1-yl)(piperidin-1-yl)methanone 9 (100 mg, 224 μmol) in chloroform (2 mL) was added 2,2,2-trichloroacetyl isocyanate (39 μl, 314 μmol). The reaction was stirred at RT for 1 h and deposited on 3 g of Alumina (Brockmann II). After 1 h, the product was eluted from the alumina with 10% MeOH in dichloromethane. The crude reaction product was concentrated and purified by column chromatography to afford (S)-(4-(4-(3-methyl-4-(piperidine-1-carbonyl)piperazin-1-yl)pyrido[3,4-d]pyridazin-1-yl)phenyl)methyl carbamate 10. MS 489.2 (calc'd) 490.1 (M+H, found).

Workup

  1. waitAfter 1 h
  2. washthe product was eluted from the alumina with 10% MeOH in dichloromethane
  3. customThe crude reaction product
  4. concentrationwas concentrated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-3ccf2b125af24e6d8f5fefeb3e4dac16
Source dataset
uspto-grants-2012_07
Patent number
US08222251B2

Reaction notes

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