Ammonium Chloride → 9-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide

HRID 575024Notes

Reaction equation

HRID 575024 reaction equation
[Br:1][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](O)=[O:16])=[N:8][C:7]=3[C:6]=2[CH:18]=1.[NH4+].[Cl-].CC[N:24](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCCC1>[Br:1][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]([NH2:24])=[O:16])=[N:8][C:7]=3[C:6]=2[CH:18]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866930579-Bromo-8-fluoro-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylic acid

Product 1

HCID 866930599-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamideYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 3-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of argon was placed 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid (130 g, 377.74 mmol, 1.00 equiv), NH4Cl (81.95 g, 1.53 mol, 4.08 equiv), tetrahydrofuran (1 L), DIEA (97.782 g, 756.59 mmol, 2.00 equiv), and HATU (158.08 g, 415.75 mmol, 1.10 equiv). The resulting solution was stirred at room temperature overnight and diluted with 2.5 L of ice/water. The solids were collected by filtration, washed with 4×1 L of water and dried to afford 84.2 g (65%) of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a brown solid. LC-MS: 343 [M+H]+ 1H NMR (300 MHz, DMSO, ppm) δ 3.33-3.43 (m, 2H), 4.36-4.39 (m, 2H), 7.02-7.14 (d, 1H), 7.88 (s, 1H), 8.52 (s, 1H), 8.88-8.90 (d, 1H). 19F-NMR (300 MHz, DMSO, ppm) δ 107.91 (s, 1F).

Workup

  1. customInto a 3-L 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of argon
  3. filtrationThe solids were collected by filtration
  4. washwashed with 4×1 L of water
  5. customdried

Sources & evidence

ORD record
ord-f0deb004b1b243ec9a12e1be2eb0de6c
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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