Propargyl bromide → HCID 15389019, compound

HRID 863832Notes

Reaction equation

HRID 863832 reaction equation
[C:1]([N:20]([CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[O:35][C:36]3[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=3[N:38]=2)=[CH:30][CH:29]=1)[CH2:21][CH2:22][OH:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CN1C(=O)N(C)[CH2:49][CH2:48][CH2:47]1.C(Br)C#C>C1COCC1.C1(C)C=CC=CC=1>[C:1]([N:20]([CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2[O:35][C:36]3[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=3[N:38]=2)=[CH:32][CH:33]=1)[CH2:21][CH2:22][O:23][CH2:49][C:48]#[CH:47])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7842Propargyl bromide2×HCID 24758Sodium hydride2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 15389018HCID 15389018, compound

Product 1

HCID 15389019HCID 15389019, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dry N-trityl-N-[2-(4-(benzoxazol-2-yl)benzyloxy)ethyl]-2-hydroxyethanamine (8.7 g; 15.7 mmol) is dissolved in THF (50 ml). NaH (1 g; 25 mmol) is added and stirred vigorously at 0° C. for 1 minute then brought to room temperature for 45 minutes. DMPU [1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone] (5 ml) is added followed by propargyl bromide (80 wt %/toluene; 2.1 ml) and stirred for 48 hours. To this is added 0.6 g NaH and 1.5 ml propargyl bromide. After stirring vigorously, an additional 48 hours the reaction mixture is quenched with MeOH, concentrated and purified by column chromatography using 10 Et3N/10 CH2Cl2 /80 petroleum ether. The product is triturated with ether to give solid N-trityl-N-[2-(4-(benzoxazol-2-yl)benzyloxy)ethyl]-2-(prop-2-ynyloxy)ethanamine which is used directly in Step F.

Workup

  1. waitthen brought to room temperature for 45 minutes
  2. stirringstirred for 48 hours
  3. stirringAfter stirring vigorously, an additional 48 hours the reaction mixture
  4. customis quenched with MeOH
  5. concentrationconcentrated
  6. custompurified by column chromatography
  7. customThe product is triturated with ether

Sources & evidence

ORD record
ord-e5b2658d9dcf4bffa2c457eebaa4d2c5
Source dataset
uspto-grants-1996_10
Patent number
US05561143

Reaction notes

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