3-Acetamidobenzoic acid → 3-acetylamino-N-{3-cyano-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-benzamide

HRID 1796678Notes

Reaction equation

HRID 1796678 reaction equation
Cl.[NH2:2][C:3]1[C:4]([CH3:30])=[C:5]2[C:10]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][CH3:26])=[CH:14][CH:13]=3)=[C:9]([C:27]#[N:28])[CH:8]=[N:7][N:6]2[CH:29]=1.[C:31]([NH:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38](O)=[O:39])(=[O:33])[CH3:32].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:31]([NH:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38]([NH:2][C:3]1[C:4]([CH3:30])=[C:5]2[C:10]([NH:11][C:12]3[CH:13]=[CH:14][C:15]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[O:25][CH3:26])=[CH:16][CH:17]=3)=[C:9]([C:27]#[N:28])[CH:8]=[N:7][N:6]2[CH:29]=1)=[O:39])(=[O:33])[CH3:32]

Participants

7

Reactant 4

HCID 488473-Acetamidobenzoic acidHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 221794246-Amino-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazine-3-carbonitrile hydrochloride

Product 1

HCID 221795123-acetylamino-N-{3-cyano-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-benzamideYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 430F (42 mg, 0.10 mmol), 3-acetylamino-benzoic acid (27 mg, 0.15 mmol), PyBrop (73 mg, 0.15 mmol) and DIEA 70 μl, 0.40 mmol) in DMF (1 ml) was stirred at room temperature for 16 h under argon. Treated with EtOAc (30 ml), the mixture was washed with H2O (3×10 ml) and brine (10 ml), dried with Na2SO4. Removal of the solvent followed by flash chromatography of the residue on silica gel (50% EtOAc-CH2Cl2) gave 430 (38 mg, 70%) as a light yellow solid. It has a retention time of 6.16 min (standard LC1 method, 8 min run). MS Found: (M+H)+=547.2

Workup

  1. washthe mixture was washed with H2O (3×10 ml) and brine (10 ml)
  2. dry with materialdried with Na2SO4
  3. customRemoval of the solvent

Sources & evidence

ORD record
ord-26bc5bf6bc28445981455db1acc77aa3
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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