Trimethyl orthoformate → HCID 59277790, compound

HRID 341180Notes

Reaction equation

HRID 341180 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:11][C:10]=2[NH2:22])[CH:5]=[CH:6][CH:7]=1.[CH3:23]OC(OC)OC>C(Cl)Cl>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:12]2[CH:13]=[CH:14][C:9]3[N:8]([C:4]4[CH:3]=[C:2]([NH2:1])[CH:7]=[CH:6][CH:5]=4)[CH:23]=[N:22][C:10]=3[CH:11]=2)=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 9005Trimethyl orthoformateHCID 59277816HCID 59277816, compound

Product 1

HCID 59277790HCID 59277790, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of N*4*-(3-Amino-phenyl)-4′-fluoro-biphenyl-3,4-diamine (Procedure O3, ˜5.1 mmol) in trimethylorthoformate (30 ml) was stirred and heated at 120° C. under N2 for 10 hours. The volatiles were removed in vacuo and the residue was taken up in EtOH (30 ml) and treated with c.HCl (2 ml), then stirred and heated at reflux for 3 hours. After cooling to RT, the mixture was concentrated to ˜2 ml, then diluted with H2O. NaHCO3 (sat) was added to give ˜pH7.5. The solid was taken up in CH2Cl2. The organic layer was dried and evaporated. The residue was purified by chromatography on silica (0%→1%→>2% 2M NH3-MeOH/CH2Cl2). The material was then triturated with Et2O to give the title compound (890 mg) as an off-white solid.

Workup

  1. customThe volatiles were removed in vacuo
  2. additiontreated with c
  3. temperatureheated
  4. temperatureat reflux for 3 hours
  5. temperatureAfter cooling to RT
  6. concentrationthe mixture was concentrated to ˜2 ml
  7. additiondiluted with H2O
  8. additionNaHCO3 (sat) was added
  9. customto give ˜pH7.5
  10. customThe organic layer was dried
  11. customevaporated
  12. customThe residue was purified by chromatography on silica (0%→1%→>2% 2M NH3-MeOH/CH2Cl2)
  13. customThe material was then triturated with Et2O

Sources & evidence

ORD record
ord-20e5ba8e599b4fda863b1e856692a66e
Source dataset
uspto-grants-2014_11
Patent number
US08895745B2

Reaction notes

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