2-Methyl-3-butyn-2-ol → 8-Fluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

HRID 575090Notes

Reaction equation

HRID 575090 reaction equation
Br[C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]([NH2:17])=[O:16])=[N:8][C:7]=3[C:6]=2[CH:18]=1.[CH3:20][C:21]([OH:25])([C:23]#[CH:24])[CH3:22]>CS(C)=O.C(N(CC)CC)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:19][C:3]1[C:2]([C:24]#[C:23][C:21]([OH:25])([CH3:22])[CH3:20])=[CH:18][C:6]2[C:7]3[N:8]=[C:9]([C:15]([NH2:17])=[O:16])[S:10][C:11]=3[CH2:12][CH2:13][O:14][C:5]=2[CH:4]=1

Participants

7

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 866930599-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide

Product 1

HCID 866931198-Fluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Procedure

The title compound was prepared according to a procedure similar to that described in Procedure G. Into a 8-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed a suspension of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide (300 mg, 0.87 mmol, 1.00 equiv), 2-methylbut-3-yn-2-ol (260 mg, 3.09 mmol, 3.50 equiv) and Pd(PPh3)2Cl2 (60 mg, 0.09 mmol, 0.10 equiv) in DMSO (1 mL) and triethylamine (1 mL). The final reaction mixture was irradiated with microwave radiation for 1 h at 70° C. The resulting solution was diluted with 20 mL of water. The solids were collected by filtration and washed with 20 mL of ethyl acetate. This resulted in 0.24 g (79%) of 8-Fluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid. LC-MS (ES, m/z): 347[M+H]+; 1H-NMR: (300 MHz, DMSO-d6, ppm) δ 8.652 (d, 1H), 8.460 (s, 1H), 7.860 (s, 1H), 7.007 (d, 1H), 5.497 (s, 1H), 4.391 (t, 2H), 3.414 (t, 2H), 1.491 (s, 6H).

Workup

  1. customInto a 8-mL sealed tube
  2. custompurged
  3. temperaturemaintained with an inert atmosphere of nitrogen
  4. customThe final reaction mixture
  5. customwas irradiated with microwave radiation for 1 h at 70° C
  6. filtrationThe solids were collected by filtration
  7. washwashed with 20 mL of ethyl acetate
  8. customThis resulted in 0.24 g (79%) of 8-Fluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid

Sources & evidence

ORD record
ord-54ee7af7eabd4419b76da5c86b629a24
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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