Cesium hydroxide → 5-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1910672Notes

Reaction equation

HRID 1910672 reaction equation
Cl[C:2]1[C:3]2[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=2[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:6](=[O:17])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:8]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[N:44][CH:45]=2)O1.[OH-].[Cs+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:46][C:42]1[CH:41]=[C:40]([C:2]2[C:3]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=3[N:5]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[C:6](=[O:17])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:8]=2)[CH:45]=[N:44][CH:43]=1

Participants

7

Reactant 3

HCID 62750Cesium hydroxideHCID 438110685-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamineHCID 595943935,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 672834995-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 33.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (240 mg) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (134 mg, 1.2 eq) were suspended in dioxane/water (6 mL/2 mL), and then cesium hydroxide (170 mg, 2 eq) was added and the mixture was degassed by pulling vacuum until bubbling occurred, and then introducing nitrogen gas. The degassing procedure was repeated twice, and then tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.05 eq) was added. The degassing procedure was repeated once, and then the reaction was heated to 90° C. for three hours. The crude mixture was then diluted with EtOAc (20 mL) and then washed with water, then brine, and then it was dried over sodium sulfate, and concentrated onto silica gel. The product was purified by chromatography (gradient: 75:25 hexanes:EtOAc to EtOAc) delivering the product as a solid (90 mg, 33% yield). MS (ES+) m/z 531.0 (M+1).

Workup

  1. customthe mixture was degassed
  2. customuntil bubbling
  3. washwashed with water
  4. dry with materialbrine, and then it was dried over sodium sulfate
  5. concentrationconcentrated onto silica gel
  6. customThe product was purified by chromatography (gradient: 75:25 hexanes:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-17cd510d39ee491b9fc8a42fdd7f94d5
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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