Lithium Chloride → HCID 46946832, compound

HRID 1910697Notes

Reaction equation

HRID 1910697 reaction equation
Cl[C:2]1[C:3]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:4]=2[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)[N:8]=1.[NH2:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][N:29]=1.[Cl-].[Li+].O.[OH-].[Cs+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.O1CCOCC1>[NH2:27][C:28]1[N:29]=[CH:30][C:31]([C:2]2[C:3]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:4]=3[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:11]=3)[N:8]=2)=[CH:32][CH:33]=1

Participants

8

Reactant 4

HCID 433294Lithium ChlorideHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 23679066Caesium hydroxide--water (1/1/1)HCID 67283855HCID 67283855, compound

Product 1

HCID 46946832HCID 46946832, compoundYield 30.5%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5,7-Dichloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.40 g, 1.04 mmol), 2-aminopyridine-5-boronic acid pinacol ester (0.28 g, 1.25 mmol) and lithium chloride (0.13 g, 3.1 mmol) were added to 1,4-dioxane (4 mL). Nitrogen was bubbled into solution as reagents were added. Tetrakis(triphenylphosphine) palladium(0) (0.12 g, 0.10 mmol) was added followed by cesium hydroxide monohydrate (0.53 g, 3.1 mmol) and water (1 mL). After bubbling through nitrogen for 5 minutes the reaction was heated to 100° C. for 1 h under a nitrogen atmosphere. The mixture was cooled to ambient temperature, diluted with ethyl acetate (25 mL), washed with water (2×20 mL), brine (20 mL), dried with sodium sulfate, decanted then concentrated in the presence of silica. Chromotography eluting with a gradient of 30-100% ethyl acetate in hexanes provided 5-(6-aminopyridin-3-yl)-7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (140 mg, 30% yield). 1H NMR (300 MHz, d6-DMSO) δ 3.47 (m, 2H) 3.75 (m, 1H), 6.43 (m, 1H), 6.50 (s, 2H), 7.27 (m, 1H), 7.40-7.67 (m, 6H), 7.75-7.82 (m, 4H), 7.92 (m, 1H); ESI m/z measured 441.1487 [M+H]+. calculated 441.1482.

Workup

  1. customNitrogen was bubbled into solution as reagents
  2. additionwere added
  3. customAfter bubbling through nitrogen for 5 minutes the reaction
  4. temperatureThe mixture was cooled to ambient temperature
  5. additiondiluted with ethyl acetate (25 mL)
  6. washwashed with water (2×20 mL), brine (20 mL)
  7. dry with materialdried with sodium sulfate
  8. customdecanted
  9. concentrationthen concentrated in the presence of silica
  10. washChromotography eluting with a gradient of 30-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c51a88618eaf43ea9f9237798a5a80f7
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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