Sodium Carbonate → HCID 86674688, compound

HRID 571830Notes

Reaction equation

HRID 571830 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][C:3]=1[Br:21].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[C:34](=[O:37])([O-])[O-].[Na+].[Na+].[Cl:40][C:41]1[N:46]=[CH:45][C:44]([NH2:47])=[CH:43][CH:42]=1>ClCCl.O>[C:17]([O:16][C:14]([N:10]1[CH2:11][CH2:12][O:13][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:34]([NH:47][C:44]3[CH:45]=[N:46][C:41]([Cl:40])=[CH:42][CH:43]=3)=[O:37])=[C:3]([Br:21])[CH:4]=2)[CH2:9]1)=[O:15])([CH3:18])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 793055-Amino-2-chloropyridineHCID 94429TriphosgeneHCID 71743185Tert-butyl 2-(4-amino-3-bromophenyl)morpholine-4-carboxylate

Product 1

HCID 86674688HCID 86674688, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of tert-butyl (RS)-2-(4-amino-3-bromophenyl)morpholine-4-carboxylate (100 mg, example 28a) in dichloromethane (2 ml) was added triphosgene (31 mg). A solution of sodium carbonate (59 mg) in water (2 ml) was then added. The reaction mixture was stirred at room temperature for 2.5 hours. TLC showed all the starting material had reacted. A solution of 6-chloropyridin-3-amine (36 mg, CAS 5350-93-6) in dichloromethane (2 ml) was then added and the reaction mixture was stirred at room temperature for a further 2 hours. TLC showed the reaction was complete. The reaction mixture was poured into dichloromethane and extracted with water. The organic phase was separated, dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: 0% to 80% EtOAc in heptanes) to give (RS)-2-{3-bromo-4-[3-(6-chloro-pyridin-3-yl)-ureido]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (47 mg, 33%) as an off-white solid. MS (ISP): 515.2 ([{37Cl81Br}M+H]+), 513.2 ([{37Cl79Br or 35Cl81Br}M+H]+), 511.0 ([{35Cl79Br}M+H]+), 459.0 ([{37Cl81Br}M+H—C4H8]+), 457.0 ([{37Cl79Br or 35Cl81Br}M+H—C4H8]+), 454.9 ([{35Cl79Br}M+H—C4H8]+).

Workup

  1. customhad reacted
  2. stirringthe reaction mixture was stirred at room temperature for a further 2 hours
  3. extractionextracted with water
  4. customThe organic phase was separated
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2; gradient: 0% to 80% EtOAc in heptanes)

Sources & evidence

ORD record
ord-59b1904a7b874ea6b0b6da6ef5923736
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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