Cesium fluoride → tert-Butyl (1-{4-[2-(1,3-benzothiazol-2-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate

HRID 1047064Notes

Reaction equation

HRID 1047064 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:7]3[N:15]=[CH:16][CH:17]=[CH:18][C:6]=3[N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.C([Sn](CCCC)(CCCC)[C:43]1[S:44][C:45]2[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=2[N:47]=1)CCC.[F-].[Cs+]>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[S:44]1[C:45]2[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=2[N:47]=[C:43]1[C:2]1[N:3]=[C:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:7]3[N:15]=[CH:16][CH:17]=[CH:18][C:6]=3[N:5]2[C:19]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]2([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 37623922-(Tributylstannyl)-1,3-benzothiazoleHCID 136331865tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 69087701tert-Butyl (1-{4-[2-(1,3-benzothiazol-2-yl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamateYield 45.2%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of tert-butyl {1-[4-(2-bromo-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (50.0 mg, 0.0895 mmol), 2-(tributylstannyl)-1,3-benzothiazole (76.0 mg, 0.179 mmol), bis (tri-tert-butylphosphine)palladium(0) (9.15 mg, 0.0179 mmol) and cesium fluoride (88.4 mg, 0.582 mmol) in dioxane (1.00 mL) was heated at 130° C. under microwave irradiation for 2 hours under nitrogen. After cooling to room temperature, the mixture was diluted with water and extracted with EtOAc (×3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (EtOAc/hexane=4:1→2:1→1:1) and PTLC (DCM/EtOAc=95:5) to afford desired product (24.8 mg, 45.2%) as pale yellow solid. 1HNMR (CDCl3) 500 MHz δ: 8.23 (dd, J=7.7, 1.4 Hz, 1H), 8.06-8.01 (m, 1H), 7.96 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.53-7.38 (m, 5H), 7.36-7.29 (m, 2H), 7.17 (td, J=7.4, 1.1 Hz, 1H), 6.99-6.96 (m, 1H), 6.93-6.85 (m, 1H), 6.62 (dd, J=8.0, 4.6 Hz, 1H), 6.49-6.45 (m, 1H), 5.20 (br s, 1H), 2.69-2.26 (m, 4H), 2.21-2.09 (m, 1H), 1.97-1.85 (m, 1H), 1.41 (br s, 9H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc (×3)
  3. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (EtOAc/hexane=4:1→2:1→1:1) and PTLC (DCM/EtOAc=95:5)

Sources & evidence

ORD record
ord-b229a5c4edd84f21a216b4b0faf901d3
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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