Cesium carbonate → {3-[3-(5-Acetyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-ylamino]-propyl}-methyl-carbamic acid tert-butyl ester

HRID 870627Notes

Reaction equation

HRID 870627 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].F[C:8]1[CH:9]=[CH:10][C:11]2[N:12]([C:14]([C:17]3[S:21][C:20]([C:22](=[O:24])[CH3:23])=[CH:19][CH:18]=3)=[CH:15][N:16]=2)[N:13]=1.[C:25]([O:29][C:30](=[O:37])[N:31]([CH2:33][CH2:34][CH2:35][NH2:36])[CH3:32])([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O>[C:25]([O:29][C:30](=[O:37])[N:31]([CH2:33][CH2:34][CH2:35][NH:36][C:8]1[CH:9]=[CH:10][C:11]2[N:12]([C:14]([C:17]3[S:21][C:20]([C:22](=[O:24])[CH3:23])=[CH:19][CH:18]=3)=[CH:15][N:16]=2)[N:13]=1)[CH3:32])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2756543tert-butyl N-(3-aminopropyl)-N-methylcarbamateHCID 866963171-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

Product 1

HCID 86696325{3-[3-(5-Acetyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-ylamino]-propyl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cesium carbonate [534-17-8] (125 mg, 0.4 mmol) was added to a solution of 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone (50 mg, 0.2 mmol) and N-(3-aminopropyl)-N-methylcarbamic acid tert-butyl ester [150349-36-3] (72 mg, 0.4 mmol) in N,N-dimethylformamide (1.5 mL) and stirred overnight at ambient temperature then partitioned between ethyl acetate and water. The organic extract was evaporated and product isolated by preparative RP-HPLC to provide {3-[3-(5-acetyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-ylamino]-propyl}-methyl-carbamic acid tert-butyl ester as a yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.33-1.49 (m, 9H) 2.04 (d, J=11.87 Hz, 2H) 2.59 (s, 3H) 2.91 (s, 3H) 3.35-3.53 (m, 4H) 4.62 (s, 1H) 6.75 (d, J=9.60 Hz, 1H) 7.64-7.75 (m, 2H) 7.87 (d, J=4.04 Hz, 1H) 7.98 (s, 1H). LRMS (ESI) m/z 430.2 [(M+H)]+, calc'd for C21H27N5O3S: 429.55.

Workup

  1. customthen partitioned between ethyl acetate and water
  2. extractionThe organic extract
  3. customwas evaporated
  4. customproduct isolated by preparative RP-HPLC

Sources & evidence

ORD record
ord-dc141ad481de451286158053e7deec32
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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