Pyridine → HCID 486695, compound

HRID 369743Notes

Reaction equation

HRID 369743 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:18])([C:13]#[C:14][CH:15]2[CH2:17][CH2:16]2)[C:9]([F:12])([F:11])[F:10])=[CH:6][C:5]([Cl:19])=[CH:4][CH:3]=1.N1C=CC=CC=1.Br[C:27]([CH3:32])([CH3:31])[C:28](Cl)=O.C[CH2:34][O:35]CC>>[Cl:19][C:5]1[CH:4]=[CH:3][C:2]2[NH:1][C:34](=[O:35])[C@H:28]([CH:27]([CH3:32])[CH3:31])[O:18][C@:8]([C:13]#[C:14][CH:15]3[CH2:16][CH2:17]3)([C:9]([F:10])([F:11])[F:12])[C:7]=2[CH:6]=1

Participants

5

Reactant 4

HCID 1049PyridineHCID 3283Diethyl Ether2×HCID 98389352-(2-Amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-olHCID 111060492-Bromo-2-methylpropanoyl chloride

Product 1

HCID 486695HCID 486695, compound

Procedure

To a stirred ice-cooled solution of 290 mg of 6-amino-3-chloro-α-cyclopropylethynyl-α-(trifluoromethyl)benzyl alcohol (Example 14, Part A) in 15 mL of dry ether was added 0.100 mL of dry pyridine and 228 mg of α-bromoisobutyryl chloride. After 30 min, the reaction mixture was diluted with ether, washed with water and aqueous sodium bicarbonate, dried and evaporated. The residue was dissolved in 15 mL of dry DMF, 268 mg of lithium iodide and 978 mg of cesium carbonate was added, and the resulting heterogeneous mixture was stirred at room temperature overnight. The reaction mixture was then poured onto water and etracted twice with ether. The combined extracts were washed with water and brine, dried and evaporated. Since TLC. showed the reaction had only gone halfway to completion, the crude product was redissloved in 15 mL of DMF and subjected to the same reaction conditions as above for another 24 h. After the same work-up, the crude product was purified by column chromatography over silica gel (elution with 5-15% ethyl acetate in hexanes) and then recrystallized from ethyl acetate/hexanes to give 45 mg of the title compound as colorless crystals: mp 167°; Anal. Calcd. for C18H17NO2F3Cl: C, 58.15; H, 4.62; N, 3.78. Found: C, 58.11; H, 4.59; N, 3.70.

Workup

  1. washwashed with water and aqueous sodium bicarbonate
  2. customdried
  3. customevaporated
  4. dissolutionThe residue was dissolved in 15 mL of dry DMF
  5. addition268 mg of lithium iodide and 978 mg of cesium carbonate was added
  6. additionThe reaction mixture was then poured onto water
  7. washThe combined extracts were washed with water and brine
  8. customdried
  9. customevaporated
  10. customsubjected to the same reaction conditions as above for another 24 h
  11. customAfter the same work-up, the crude product was purified by column chromatography over silica gel (elution with 5-15% ethyl acetate in hexanes)
  12. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1f0c218ef0324a00b8e62a9da1edc340
Source dataset
uspto-grants-2000_10
Patent number
US06140320

Reaction notes

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