4-Methylmorpholine → HCID 53702558, compound

HRID 1352223Notes

Reaction equation

HRID 1352223 reaction equation
[C:1](O)(=[O:7])/[CH:2]=[CH:3]/[CH:4]=[CH:5]/[CH3:6].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][CH2:38][CH:39]1[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]1)[N:31]=[CH:30][N:29]=[C:28]2[NH:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([Br:53])[CH:48]=1>O1CCCC1.N1C=CC=CC=1>[Br:53][C:49]1[CH:48]=[C:47]([NH:46][C:28]2[C:27]3[C:32](=[CH:33][C:34]([O:35][CH2:36][CH2:37][CH2:38][CH:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)=[C:25]([NH:24][C:1](=[O:7])[CH:2]=[CH:3][CH:4]=[CH:5][CH3:6])[CH:26]=3)[N:31]=[CH:30][N:29]=2)[CH:52]=[CH:51][CH:50]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 643460Sorbic AcidHCID 111906016-Amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline

Product 1

HCID 53702558HCID 53702558, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 31 mg of sorbic acid in 1 ml of tetrahydrofuran are added 40 μl of isobutyl chloroformate followed by 45 μl of N-methylmorpholine whilst cooling with an ice bath. The white suspension is stirred for one minute, then a solution of 100 mg of 6-amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline in 1.5 ml of pyridine is added. The ice bath is removed and the reaction mixture is stirred overnight. For working up, it is poured onto 20 ml of ice water, stirred for 30 minutes and adjusted to pH 9–10 with a few drops of 2 N sodium hydroxide solution. The aqueous phase is extracted with methylene chloride, the combined organic phases are dried over sodium sulfate and concentrated by evaporation. The resin-like crude product is purified by chromatography over an aluminium oxide column (activity III) with methylene chloride/methanol (99.5:0.5). Yield: 62 mg (52% of theory); Rf value: 0.29 (aluminium oxide, activity III; methylene chloride/methanol=98:2); mass spectrum (EI): m/z=563, 565 [M]+.

Workup

  1. temperaturewhilst cooling with an ice bath
  2. customThe ice bath is removed
  3. stirringthe reaction mixture is stirred overnight
  4. additionit is poured onto 20 ml of ice water
  5. stirringstirred for 30 minutes
  6. extractionThe aqueous phase is extracted with methylene chloride
  7. dry with materialthe combined organic phases are dried over sodium sulfate
  8. concentrationconcentrated by evaporation
  9. customThe resin-like crude product is purified by chromatography over an aluminium oxide column (activity III) with methylene chloride/methanol (99.5:0.5)

Sources & evidence

ORD record
ord-7ebb40a86b2d4716978c553a3edb1c9f
Source dataset
uspto-grants-2007_05
Patent number
US07220750B2

Reaction notes

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