Water → (+/-)-9-Fluoro-10-(3-hydroxy-3-(5-vinylisoxazol-3-yl)but-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575226Notes

Reaction equation

HRID 575226 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:11][C:12]1[C:28]([C:29]#[C:30][C:31]([C:34]2[CH:38]=[C:37]([CH:39]=O)[O:36][N:35]=2)([OH:33])[CH3:32])=[CH:27][C:15]2[C:16]3[N:17]([CH:21]=[C:22]([C:24]([NH2:26])=[O:25])[N:23]=3)[CH2:18][CH2:19][O:20][C:14]=2[CH:13]=1.O.[CH3:42]C#N>C1(C)C=CC=CC=1.O1CCCC1>[F:11][C:12]1[C:28]([C:29]#[C:30][C:31]([OH:33])([C:34]2[CH:38]=[C:37]([CH:39]=[CH2:42])[O:36][N:35]=2)[CH3:32])=[CH:27][C:15]2[C:16]3[N:17]([CH:21]=[C:22]([C:24]([NH2:26])=[O:25])[N:23]=3)[CH2:18][CH2:19][O:20][C:14]=2[CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6342Acetonitrile2×HCID 3251421Potassium bis(trimethylsilyl)amideHCID 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 86693233(+/-)-9-Fluoro-10-(3-hydroxy-3-(5-vinylisoxazol-3-yl)but-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamideYield 10%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of KHMDS (0.9 mL, 3.20 equiv) in toluene (0.5M) was added dropwise to a stirred solution of Ph3PCH3I (180 mg, 3.02 equiv) in tetrahydrofuran (3 mL) at 0° C. and the resulting mixture was stirred at 0° C. for 30 min. To this was added a solution of 9-fluoro-10-(3-(5-formylisoxazole-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) in tetrahydrofuran (0.2 mL) dropwise at 0° C. The resulting solution was stirred for 3 h at room temperature. The crude product 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 mmol NH4HCO3 and CH3CN (25% CH3CN up to 40% in 10 min, up to 95% in 2 min, down to 25% in 2 min); Detector, UV 254/220 nm giving the titled compound (10%) as a light yellow solid.

Workup

  1. stirringThe resulting solution was stirred for 3 h at room temperature
  2. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters))
  3. waitup to 95% in 2 min
  4. waitdown to 25% in 2 min)

Sources & evidence

ORD record
ord-6f819bce1c65478a8568b7827c2df3fc
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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