Dichloromethane → HCID 68292186, compound

HRID 1408945Notes

Reaction equation

HRID 1408945 reaction equation
ClCCl.C(N(CC)CC)C.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:19][C:20]1([CH3:45])[C:24](=O)[CH2:23][CH2:22][CH:21]1[NH:26][C:27]1[C:28]2[N:29]([CH:36]=[C:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:38]=2)[N:30]=[CH:31][C:32]=1[C:33]([NH2:35])=[O:34]>C1C=CC=CC=1.C(OCC)(=O)C.[Ti](Cl)(Cl)(Cl)Cl>[CH2:11]([N:18]=[C:24]1[CH2:23][CH2:22][CH:21]([NH:26][C:27]2[C:28]3[N:29]([CH:36]=[C:37]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH:38]=3)[N:30]=[CH:31][C:32]=2[C:33]([NH2:35])=[O:34])[C:20]1([CH3:45])[CH3:19])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 7504BenzylamineHCID 8471TriethylamineHCID 68291120HCID 68291120, compound

Product 1

HCID 68292186HCID 68292186, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 241BenzeneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 1.0 M dichloromethane solution of titanium(IV) chloride (0.025 mL, 0.025 mmol) was added to a solution of triethylamine (0.042 mL, 0.298 mmol) and benzylamine (6.39 mg, 0.060 mmol) in benzene (5 mL) at room temperature. The mixture was heated to reflux. A solution of 4-((2,2-dimethyl-3-oxocyclopentyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide (18 mg, 0.050 mmol, from Example 144) in benzene (1 mL) was added to the above mixture. The resultant mixture was kept at reflux for 3 h, cooled to room temperature, diluted with ethyl acetate (80 mL), washed with water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography, eluting with 30 to 80% ethyl acetate in hexanes, to give 4-(3-(benzylimino)-2,2-dimethylcyclopentylamino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide (7 mg, 31% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 10.66 (1 H, d, J=8.80 Hz), 7.80-8.02 (2 H, m), 7.55-7.76 (2 H, m), 7.20-7.53 (8 H, m), 7.10 (1 H, d, J=1.76 Hz), 5.59 (2 H, br. s.), 4.41-4.51 (1 H, m), 2.56-2.78 (1 H, m), 2.34-2.60 (2 H, m), 1.92-2.01 (1 H, m), 1.19-1.43 (6 H, m); MS (ES+) m/z: 452.3 (M+H).

Workup

  1. temperatureThe mixture was heated to reflux
  2. temperatureat reflux for 3 h
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 30 to 80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f7ea3494c68d4586b94f5d83b65b6fc8
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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