Triethylamine → N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]-3-[3-oxo-3-(tetrahydropyran-2-yloxyamino)prop-1-enyl]benzamide

HRID 539806Notes

Reaction equation

HRID 539806 reaction equation
[CH3:1][C:2]([CH3:37])([CH3:36])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([C:13]2[N:14]=[C:15]3[N:20]([CH:21]=2)[N:19]=[C:18]([NH:22][C:23]([C:25]2[CH:26]=[C:27]([CH:31]=[CH:32][C:33](O)=[O:34])[CH:28]=[CH:29][CH:30]=2)=[O:24])[CH:17]=[CH:16]3)[CH:9]=[CH:10][C:11]=1[CH3:12])=[O:4].[O:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH:39]1[O:44][NH2:45].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(#N)C>[CH3:1][C:2]([CH3:37])([CH3:36])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([C:13]2[N:14]=[C:15]3[N:20]([CH:21]=2)[N:19]=[C:18]([NH:22][C:23](=[O:24])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH:31]=[CH:32][C:33](=[O:34])[NH:45][O:44][CH:39]4[CH2:40][CH2:41][CH2:42][CH2:43][O:38]4)[CH:26]=2)[CH:17]=[CH:16]3)[CH:9]=[CH:10][C:11]=1[CH3:12])=[O:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 680891733-[3-[[2-[3-(2,2-Dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]carbamoyl]phenyl]prop-2-enoic acid

Product 1

HCID 86667862N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]-3-[3-oxo-3-(tetrahydropyran-2-yloxyamino)prop-1-enyl]benzamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 20-mL vial is charged with acetonitrile (0.4 mL), 3-[3-[[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]carbamoyl]phenyl]prop-2-enoic acid (0.025 g, 0.05 mmol), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.0088 g, 0.08 mmol), triethylamine (0.021 mL, 0.15 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.033 g, 0.08 mmol). The mixture is stirred at room temperature for 2 hr, concentrated and taken up into saturated aqueous Na2CO3 (2 mL), extracted with EtOAc and CH2Cl2. Organic layers are combined, dried and concentrated to give crude N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]-3-[3-oxo-3-(tetrahydropyran-2-yloxyamino)prop-1-enyl]benzamide. This is taken up in a mixture of aqueous HCl (1 mL, 1M) and MeOH (1 mL), and is stirred at 50° C. for 1 hour. The mixture is concentrated, taken up in DMSO (1 mL) and purified on a Gilson preparative HPLC (reverse phase) to afford the title compound (0.015 g). LCMS (m/z)=513.5 [M+H]+, tR=2.31 min.

Workup

  1. concentrationconcentrated
  2. extractionextracted with EtOAc and CH2Cl2
  3. customdried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-908cb717e3a745bd9f3b5516120bbb2a
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

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