Potassium Carbonate → (+/-)-10-(3-(5-Ethynylisoxazol-3-yl)-3-hydroxybut-1-yn-1-yl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575227Notes

Reaction equation

HRID 575227 reaction equation
[F:1][C:2]1[C:18]([C:19]#[C:20][C:21]([C:24]2[CH:28]=[C:27]([CH:29]=O)[O:26][N:25]=2)([OH:23])[CH3:22])=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]([NH2:16])=[O:15])[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[C:31](=O)([O-])[O-].[K+].[K+]>CO>[C:29]([C:27]1[O:26][N:25]=[C:24]([C:21]([OH:23])([CH3:22])[C:20]#[C:19][C:18]2[C:2]([F:1])=[CH:3][C:4]3[O:10][CH2:9][CH2:8][N:7]4[CH:11]=[C:12]([C:14]([NH2:16])=[O:15])[N:13]=[C:6]4[C:5]=3[CH:17]=2)[CH:28]=1)#[CH:31]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 866932329-Fluoro-10-(3-(5-formylisoxazol-3-yl)-3-hydroxybut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 86693234(+/-)-10-(3-(5-Ethynylisoxazol-3-yl)-3-hydroxybut-1-yn-1-yl)-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 21%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Dimethyl [1-(methylidyneimino)-2-oxopropyl]phosphonate (27.9 mg, 0.15 mmol, 1.00 equiv) in methanol (0.2 mL) was added dropwise to a stirred mixture of 9-fluoro-10-(3-(5-formylisoxazol-3-yl)-3-hydroxybut-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (60 mg, 0.15 mmol, 1.00 equiv) and potassium carbonate (39 mg, 0.28 mmol, 2.00 equiv) in methanol (1.5 mL) at room temperature. The resulting mixture was stirred for 12 h at room temperature and the solids were filtered out. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm, mobile phase, Water with 10 mmolNH4HCO3 and CH3CN (22% CH3CN up to 43% in 15 min, up to 95% in 2 min, down to 22% in 2 min); Detector, UV 254/220 nm to give 12.7 mg of the titled compound (21%) as a colorless solid.

Workup

  1. filtrationthe solids were filtered out
  2. customThe crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters))
  3. waitColumn, SunFire Prep C18 OBD Column, 5 um, 19*150 mm, mobile phase, Water with 10 mmolNH4HCO3 and CH3CN (22% CH3CN up to 43% in 15 min
  4. waitup to 95% in 2 min
  5. waitdown to 22% in 2 min)

Sources & evidence

ORD record
ord-dcb2595a14cf47eaa718c64b83a44cd0
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

Loading…