4-Methylmorpholine → HCID 10182317, compound

HRID 1069015Notes

Reaction equation

HRID 1069015 reaction equation
[CH3:1][S:2][S:3][CH:4]([CH3:8])[C:5](O)=[O:6].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[N:31]=[CH:30][N:29]=[C:28]2[NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([Br:42])[CH:37]=1>O1CCCC1.C(Cl)Cl.CO>[Br:42][C:38]1[CH:37]=[C:36]([NH:35][C:28]2[C:27]3[C:32](=[CH:33][CH:34]=[C:25]([NH:24][C:5](=[O:6])[CH:4]([S:3][S:2][CH3:1])[CH3:8])[CH:26]=3)[N:31]=[CH:30][N:29]=2)[CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamineHCID 21190747HCID 21190747, compound

Product 1

HCID 10182317HCID 10182317, compoundYield 49.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2 grams of disulfide acid from Example 72 in 50 mL of tetrahydrofuran was cooled in an ice bath. A 1.7 mL portion of isobutyl chloroformate followed by a 1.4 mL portion of N-methyl morpholine were added. After stirring for 5 minutes at 0° C., 1.0 grams of 6-amino 4-(3-bromoanilino)quinazoline was added. The mixture was stirred for 3 hours at 0° C. and then allowed to warm to room temperature. The reaction was quenched with water and the tetrahydrofuran was evaporated under vacuum. Addition of methylene chloride followed by washing the methylene chloride layer with water and evaporation of the solvent gave a crude product. Silica gel chromatography with methanol in methylene chloride gave 0.7 grams white solid of product.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred for 3 hours at 0° C.
  3. temperatureto warm to room temperature
  4. customThe reaction was quenched with water
  5. customthe tetrahydrofuran was evaporated under vacuum
  6. additionAddition of methylene chloride
  7. washby washing the methylene chloride layer
  8. customwith water and evaporation of the solvent
  9. customgave a crude product

Sources & evidence

ORD record
ord-8ca5f679aa2e4f5aa3b887bbdb98f809
Source dataset
uspto-grants-2001_06
Patent number
US06251912B1

Reaction notes

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