Isopropyl chloroformate → HCID 89802520, compound

HRID 870764Notes

Reaction equation

HRID 870764 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[Br:12][C:13]1[N:17]2[N:18]=[C:19]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH:23]3[CH3:28])[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.Cl[C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[Br:12][C:13]1[N:17]2[N:18]=[C:19]([N:22]3[CH2:27][CH2:26][N:25]([C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:24][CH:23]3[CH3:28])[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 86696471HCID 86696471, compound

Product 1

HCID 89802520HCID 89802520, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Hunig's base [7087-68-5] (2.1 mL, 12.1 mmol) was added to an ambient temperature, stirred suspension of 3-bromo-6-(2-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine dihydrochloride (1.1 g, 3.0 mmol) in ethyl acetate (150 mL). The suspension was stirred for 1.5 h then a 1.0M solution of isopropyl chloroformate in toluene (3.0 mL) was slowly added and the reaction allowed to proceed for 17 h then washed with brine. The ethyl acetate phase was dried (MgSO4) and evaporated. Product was purified by preparative RP-HPLC to provide 52.1 mg of racemic isopropyl 4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-3-methylpiperazine-1-carboxylate as a light yellow solid, mp. 52-54° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11 (d, J=6.57 Hz, 3H) 1.15-1.25 (m, 6H) 2.51 (dt, J=3.73, 1.80 Hz, 2H) 3.15 (dd, J=12.88, 2.78 Hz, 2H) 3.86 (d, J=13.39 Hz, 1H) 3.98 (d, J=13.39 Hz, 2H) 4.47 (br. s., 1H) 4.78-4.87 (m, 1H) 7.23 (d, J=10.10 Hz, 1H) 7.64 (s, 1H) 7.91 (d, J=10.11 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ ppm 13.53, 21.90, 42.71, 48.04, 68.05, 99.42, 110.59, 126.00, 131.15, 136.33, 154.41, 154.71. LRMS (ESI) m/z 382.0/384.0 [(M+H)]+, calc'd for C16H20BrN6O2: 382.26.

Workup

  1. stirringThe suspension was stirred for 1.5 h
  2. washthen washed with brine
  3. dry with materialThe ethyl acetate phase was dried (MgSO4)
  4. customevaporated
  5. customProduct was purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-c622285228284f3f82c249483511a256
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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