Ammonia methanol → 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide

HRID 575121Notes

Reaction equation

HRID 575121 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:26])([CH3:25])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([OH:24])([CH3:23])[CH3:22])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=O.[NH3:27].CO>C1COCC1>[OH:26][C:8]1([CH3:25])[C:7]2[S:6][C:5]([C:3]([NH2:27])=[O:2])=[N:14][C:13]=2[C:12]2[CH:15]=[C:16]([C:19]#[C:20][C:21]([OH:24])([CH3:23])[CH3:22])[CH:17]=[CH:18][C:11]=2[O:10][CH2:9]1

Participants

4

Reactant 2

HCID 21705897Ammonia methanolHCID 866931474-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

Product 1

HCID 717147254-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amideYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (312 mg, 0.84 mmol) in THF (8 mL) at room temperature, NH3/CH3OH (self-made, 8 mL) was added. The mixture was stirred at room temperature for 3 h, and then concentrated to give a residue which was purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%) to give 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as an off-white solid (212 mg, 71%). 1H NMR (400 MHz, DMSO-d6): δ 8.57 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 7.90 (s, 1H), 7.31 (dd, J1=8.3 Hz, J2=2.1 Hz, 1H), 7.07 (d, J=8.4 Hz, 1H), 6.26 (s, 1H), 5.46 (s, 1H), 4.21 (d, J=11.7 Hz, 1H), 4.01 (d, J=11.8 Hz, 1H), 1.57 (s, 3H), 1.49 (s, 6H); LC-MS (ESI & APCI): 359.2 (M+1).

Workup

  1. concentrationconcentrated
  2. customto give a residue which
  3. customwas purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%)

Sources & evidence

ORD record
ord-24e1652f05e541ab9bd19ef2608caaf0
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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