2-Methylbut-3-yn-1-ol → 2-(3-Hydroxy-3-methylbut-1-yn-1-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9-carboxamide

HRID 575196Notes

Reaction equation

HRID 575196 reaction equation
[OH:1][C:2]([CH3:24])([CH3:23])[C:3]#[C:4][C:5]1[CH:6]=[CH:7][C:8]2[O:9][CH2:10][CH2:11][C:12]3[N:13]([CH:16]=[C:17]([C:19](OC)=[O:20])[N:18]=3)[C:14]=2[N:15]=1.ClC1C=CC2OCCC3[N:34](C=C(C(OC)=O)N=3)C=2N=1.CC(C#C)CO.N.O>O1CCOCC1.O>[OH:1][C:2]([CH3:23])([CH3:24])[C:3]#[C:4][C:5]1[CH:6]=[CH:7][C:8]2[O:9][CH2:10][CH2:11][C:12]3[N:13]([CH:16]=[C:17]([C:19]([NH2:34])=[O:20])[N:18]=3)[C:14]=2[N:15]=1

Participants

7

Reactant 4

HCID 1024422-Methylbut-3-yn-1-olHCID 12896473Azane;hydrateHCID 86693202Methyl 2-chloro-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9 carboxylateHCID 86693204Methyl 2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9-carboxylate

Product 1

HCID 866932032-(3-Hydroxy-3-methylbut-1-yn-1-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9-carboxamideYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 20-mL sealed tube was placed a solution of methyl 2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9-carboxylate (100 mg, 0.31 mmol, 1.00 equiv, prepared by reaction of methyl 2-chloro-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-9-carboxylate with 2-methylbut-3-yn-ol similar to as described in General Procedure G. The crude mixture was reacted with NH3.H2O (2 mL, 37%) in 1,4-dioxane (4 mL) similar to as described in General Procedure M. The resulting solution was stirred overnight at 100° C., diluted with 10 mL of H2O, extracted with 3×50 mL of ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1): Column, silica gel; mobile phase, DCM/MeOH (100:1-10:1); Detector, UV 254 um. This resulted in 423 mg (44%) of the titled compound as a light yellow solid.

Workup

  1. customInto a 20-mL sealed tube
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by Flash-Prep-HPLC with the following conditions (CombiFlash-1)

Sources & evidence

ORD record
ord-f752236474b94cceaf91e9a499b263e3
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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