Triethylamine → 1-{4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-3-(2-morpholin-4-yl-ethyl)-urea

HRID 1796671Notes

Reaction equation

HRID 1796671 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:17]3[N:18]([CH:24]=[C:25](C(O)=O)[C:26]=3[CH3:27])[N:19]=[CH:20][C:21]=2[C:22]#[N:23])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1.CC[N:33]([CH2:36]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])=CC=1.[Si](N=[N+]=[N-])(C)(C)C.[N:62]1([CH2:68][CH2:69][NH2:70])[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:17]3[N:18]([CH:24]=[C:25]([NH:33][C:36]([NH:70][CH2:69][CH2:68][N:62]4[CH2:67][CH2:66][O:65][CH2:64][CH2:63]4)=[O:45])[C:26]=3[CH3:27])[N:19]=[CH:20][C:21]=2[C:22]#[N:23])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 78378AzidotrimethylsilaneHCID 199401P,P-Diphenylphosphinic azideHCID 4082852-MorpholinoethylamineHCID 221794404-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acid

Product 1

HCID 221796611-{4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)-phenylamino]-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazin-6-yl}-3-(2-morpholin-4-yl-ethyl)-ureaYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 428A (44 mg, 0.10 mmol), Et3N (28 μl, 0.20 mmol) and DPPA (43 μl, 0.20 mmol) in dioxane (1.5 ml) was stirred under argon overnight. TMSN3 (27 μl, 0.20 mmol) was added and the mixture was heated to 80° C. for 2 h, then cooled to rt. 2-Morpholin-4-yl-ethylamine (26 μl, 0.20 mmol) was added and the mixture was heated to 80° C. for 2 h, then cooled to rt. Removal of the solvent followed by flash chromatography of the residue on silica gel (3%-5% MeOH—CH2Cl2) gave a gray solid. Recrystalization of the solid in CH2Cl2/pentane gave 428 (43 mg, 75%) as a light yellow solid. It has a retention time of 3.93 min (standard LC1 method, 8 min run). MS Found: (M+H)+=566.1

Workup

  1. temperaturecooled to rt
  2. temperaturethe mixture was heated to 80° C. for 2 h
  3. temperaturecooled to rt
  4. customRemoval of the solvent
  5. customgave a gray solid
  6. customRecrystalization of the solid in CH2Cl2/pentane

Sources & evidence

ORD record
ord-b0fe725b0e044b2abf676f5192d53e82
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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