Propargyl alcohol → HCID 136068452, compound

HRID 2189216Notes

Reaction equation

HRID 2189216 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[NH:19][C@H:20]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]1.[CH2:32]([OH:35])[C:33]#[CH:34].C(N(CC)CC)C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:7]1[N:6]=[C:5]([NH:19][C@H:20]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH2:21]2)[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:34]#[C:33][CH2:32][OH:35])[CH:3]=2)[N:8]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 136068485HCID 136068485, compound

Product 1

HCID 136068452HCID 136068452, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Tetrakis(triphenylphosphine)palladium (0.030 g, 0.026 mmol) was added to a solution of (S)-tert-butyl 3-(6-bromo-2-(2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate (prepared as described in Synthesis 32-A, 0.250 g, 0.515 mmol), propargyl alcohol (0.043 g, 0.773 mmol) and triethylamine (0.108 mL, 0.773 mmol) in THF (2.5 mL) and the solution heated to reflux for 16 hours. The mixture was cooled then purified by ion exchange chromatography on SCX-2 Isolute acidic resin (5 g), eluting with methanol and then 1 M ammonia in methanol. Further purification by column chromatography, eluting with 5% methanol in dichloromethane, gave the title compound as a solid (0.100 g, 42%).

Workup

  1. temperaturethe solution heated
  2. temperatureto reflux for 16 hours
  3. temperatureThe mixture was cooled
  4. customthen purified by ion exchange chromatography on SCX-2 Isolute acidic resin (5 g)
  5. washeluting with methanol
  6. customFurther purification by column chromatography
  7. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-9f1215bb5f3e4728b0dfa99a63890a30
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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