Benzyl Alcohol → {3-Cyano-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-carbamic acid benzyl ester

HRID 1796677Notes

Reaction equation

HRID 1796677 reaction equation
[C:1]([C:3]1[CH:8]=[N:7][N:6]2[CH:9]=[C:10](C(O)=O)[C:11]([CH3:12])=[C:5]2[C:4]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][CH3:31])=[CH:19][CH:18]=1)#[N:2].CC[N:34]([CH2:37]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])=CC=1.[CH2:56]([OH:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>O1CCOCC1.CCOC(C)=O>[CH2:56]([O:63][C:37](=[O:46])[NH:34][C:10]1[C:11]([CH3:12])=[C:5]2[C:4]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])=[CH:21][CH:22]=3)=[C:3]([C:1]#[N:2])[CH:8]=[N:7][N:6]2[CH:9]=1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 221796673-Cyano-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acid

Product 1

HCID 20791573{3-Cyano-4-[4-(2-methoxy-phenoxy)-phenylamino]-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-carbamic acid benzyl esterYield 75.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 430D (1.24 g, 3.0 mmol), Et3N (1.67 ml, 12.0 mmol) and DPPA (1.29 ml, 6.0 mmol) in 1,4-dioxane (20 ml) was stirred at rt for 16 h under argon. Benzyl alcohol (1.86 ml, 18.0 mmol) was added. The resulting mixture was heated to 80° C. for 2.5 h, cooled to rt. Removal of the solvent in vacuo gave a brown oil. Treated with EtOAc (100 ml), the mixture was washed with H2O (3×30 ml) and brine (20 ml), dried with Na2SO4. Removal of the solvent followed by flash chromatography of the residue on silica gel (CH2Cl2 first, then 20% EtOAc-hexanes) gave 430E (1.17 g, 75%) as a light yellow solid. It has a retention time of 6.96 min (standard LC1 method, 8 min run). MS Found: (M+H)+=520.2

Workup

  1. temperatureThe resulting mixture was heated to 80° C. for 2.5 h
  2. temperaturecooled to rt
  3. customRemoval of the solvent in vacuo
  4. customgave a brown oil
  5. washthe mixture was washed with H2O (3×30 ml) and brine (20 ml)
  6. dry with materialdried with Na2SO4
  7. customRemoval of the solvent

Sources & evidence

ORD record
ord-aed8b583dfdf470c9370ed17e993304f
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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