Diethyl Ether → Zeneca ZM 224832

HRID 1111328Notes

Reaction equation

HRID 1111328 reaction equation
[NH2:1][C:2]1[C:3]([C:10]([NH:12][CH2:13][CH2:14][N:15]([CH2:17][CH2:18][NH2:19])[CH3:16])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1.[Br:20][C:21]1[C:22]([OH:34])=[C:23]([CH:32]=O)[C:24]2[CH2:25][CH2:26][C:27]([CH3:31])([CH3:30])[C:28]=2[CH:29]=1.[BH4-].[Na+].CCOCC>C(O)C.C(Cl)Cl>[NH2:1][C:2]1[C:3]([C:10]([NH:12][CH2:13][CH2:14][N:15]([CH2:17][CH2:18][NH:19][CH2:32][C:23]2[C:22]([OH:34])=[C:21]([Br:20])[CH:29]=[C:28]3[C:24]=2[CH2:25][CH2:26][C:27]3([CH3:31])[CH3:30])[CH3:16])=[O:11])=[N:4][C:5]([Cl:9])=[C:6]([NH2:8])[N:7]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 4311764Sodium borohydrideHCID 22152287HCID 22152287, compoundHCID 221522956-Bromo-1,1-dimethyl-5-hydroxyindan-4-carboxaldehyde

Product 1

HCID 195507Zeneca ZM 224832Yield 77%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1.82 g (6.32 mmol) of 3,5-diamino-N-[2-[(2-aminoethyl)methylamino]ethyl]-6 -chloropyrazinecarboxamide (A) and 1.70 g (6.32 mmol) of 6-bromo-1,1-dimethyl-5-hydroxyindan-4-carboxaldehyde (B) in 70 ml of ethanol and 10 ml of methylene chloride was stirred at ambient temperature for 1 h. Sodium borohydride (0.29 g, 7.58 mmol) was added and the reaction mixture stirred for 15 min. The solution was evaporated and the residue was partitioned between water and methylene chloride The organic phase was dried and evaporated. The residue was chromatographed on silica gel (150 g) using 0.2:3:96.8 (v/v/v) ammonium hydroxide:methanol:methylene chloride as eluent. There was obtained 2.62 g (4.84 mmol, 77%) of the title compound after trituration with ether: mp 134°-136° C.

Workup

  1. stirringthe reaction mixture stirred for 15 min
  2. customThe solution was evaporated
  3. customthe residue was partitioned between water and methylene chloride The organic phase
  4. customwas dried
  5. customevaporated
  6. customThe residue was chromatographed on silica gel (150 g)

Sources & evidence

ORD record
ord-e2df3113f06e40f8943cad1f83c218d0
Source dataset
uspto-grants-1990_12
Patent number
US04980352

Reaction notes

Loading…