Diethyl Ether → HCID 68699625, compound

HRID 644081Notes

Reaction equation

HRID 644081 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:8]=[C:7]2[C:18]1[N:22]=[C:21]([CH2:23][OH:24])[S:20][N:19]=1.ClCCl.C(OCC)C.[CH3:33][N:34](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:12]1([CH2:11][N:9]2[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[C:33]#[N:34])[C:7]([C:18]3[N:22]=[C:21]([CH2:23][OH:24])[S:20][N:19]=3)=[CH:8]2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 6344DichloromethaneHCID 68697265HCID 68697265, compound

Product 1

HCID 68699625HCID 68699625, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A suspension of [3-(7-bromo-1-cyclohexylmethyl-1H-indol-3-yl)-[1,2,4]thiadiazol-5-yl]-methanol (prepared from 7-bromoindole as described in Example 7; 2×250 mg, 0.16 mmol), zinc (II) cyanide (2×72 mg, 0.61 mmol) and tetrakis(triphenylphosphine)-palladium(0) (2×21 mg, 18.3 μmol) in DMF (2×4 ml) was subjected to microwave irradiation at 200° C. for 5 min using an Emrys™ Optimizer EXP. The reactions were combined and poured into a separating funnel, to this was added dichloromethane (˜50 ml). The organics were washed successively with water (2×20 ml), 1M aqueous HCl (20 ml) and brine (20 ml), dried over magnesium sulfate, filtered, and the solvent removed in vacuo. The resulting oil was purified by flash column chromatography eluting with 50-100% (v/v) dichloromethane in heptane and then diethyl ether to give 1-cyclohexylmethyl-3-(5-hydroxymethyl-[1,2,4]thiadiazol-3-yl)-1H-indole-7-carbonitrile (416 mg, 1.18 mmol) as a light yellow oil which crystallised on standing.

Workup

  1. customirradiation at 200° C. for 5 min
  2. additionpoured into a separating funnel
  3. washThe organics were washed successively with water (2×20 ml), 1M aqueous HCl (20 ml) and brine (20 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe resulting oil was purified by flash column chromatography
  8. washeluting with 50-100% (v/v) dichloromethane in heptane

Sources & evidence

ORD record
ord-7487a3eaddc44ca1b6af7b1b1d30c10f
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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