Methyl chloroformate → HCID 57657626, compound

HRID 1514386Notes

Reaction equation

HRID 1514386 reaction equation
[NH2:1][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]([CH:23]4[CH2:28][CH2:27][C:26]([F:30])([F:29])[CH2:25][CH2:24]4)=[O:22])[C@@H:17]([CH3:31])[CH2:16]3)=[C:11]3[CH:32]=[N:33][CH:34]=[CH:35][C:10]=23)=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.Cl[C:46]([O:48][CH3:49])=[O:47]>CN(C=O)C.C(OCC)(=O)C>[F:29][C:26]1([F:30])[CH2:27][CH2:28][CH:23]([C:21]([N:18]2[CH2:19][CH2:20][N:15]([C:12]3[N:13]=[N:14][C:9]([C:6]4[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:46](=[O:47])[O:48][CH3:49])=[CH:8][CH:7]=4)=[C:10]4[CH:35]=[CH:34][N:33]=[CH:32][C:11]=34)[CH2:16][C@@H:17]2[CH3:31])=[O:22])[CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 57657594HCID 57657594, compound

Product 1

HCID 57657626HCID 57657626, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-(4-(1-(4-(aminomethyl)phenyl)pyrido[3,4-d]pyridazin-4-yl)-2-methylpiperazin-1-yl)(4,4-difluorocyclohexyl)methanone 51 (120 mg, 250 μmol) was dissolved in DMF (3 ml) and N,N-diisopropylethylamine (0.300 ml, 1.72 mmol). Methyl chloroformate (0.0211 ml, 275 μmol) was added and the reaction stirred at RT for 2 hours. The reaction was the taken up in ethyl acetate (80 ml) and washed with aqueous K2CO3 (10%), water, and brine. The organic phase was dried (MgSO4) and evaporated to give an orange oil. The residue was chromatographed over silica with a gradient of dichloromethane with 2.5% triethylamine and 0-5% methanol. The product (S)-methyl (4-(4-(4-(4,4-difluorocyclohexanecarbonyl)-3-methylpiperazin-1-yl)pyrido[3,4-d]pyridazin-1-yl)phenyl)methylcarbamate 52 was isolated as a yellow solid. LC/MS m/z=539 (M+H+).

Workup

  1. washwashed with aqueous K2CO3 (10%), water, and brine
  2. dry with materialThe organic phase was dried (MgSO4)
  3. customevaporated
  4. customto give an orange oil
  5. customThe residue was chromatographed over silica with a gradient of dichloromethane with 2.5% triethylamine and 0-5% methanol

Sources & evidence

ORD record
ord-3437fe57502147f1b30d5cb259bf7b5a
Source dataset
uspto-grants-2012_07
Patent number
US08222251B2

Reaction notes

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