Diisopropylethylamine → HCID 59725890, compound

HRID 1912831Notes

Reaction equation

HRID 1912831 reaction equation
[C:1]([O:5][C:6](=[O:12])[N:7]([CH2:9][CH2:10][OH:11])C)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.[NH2:35][C:36]1[N:44]=[CH:43][N:42]=[C:41]2[C:37]=1[N:38]=[CH:39][N:40]2[C:45]1[CH:50]=[CH:49][C:48]([NH:51][C:52]([NH:54][C:55]2[CH:60]=[CH:59][C:58]([Cl:61])=[C:57]([C:62]([F:65])([F:64])[F:63])[CH:56]=2)=[O:53])=[CH:47][CH:46]=1>C(Cl)Cl.N1C=CC=CC=1>[C:1]([O:5][C:6]([NH:7][CH2:9][CH2:10][O:11][C:23](=[O:25])[NH:35][C:36]1[N:44]=[CH:43][N:42]=[C:41]2[C:37]=1[N:38]=[CH:39][N:40]2[C:45]1[CH:46]=[CH:47][C:48]([NH:51][C:52]([NH:54][C:55]2[CH:60]=[CH:59][C:58]([Cl:61])=[C:57]([C:62]([F:64])([F:65])[F:63])[CH:56]=2)=[O:53])=[CH:49][CH:50]=1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 545700N-(tert-Butoxycarbonyl)-N-methyl-2-aminoethanolHCID 231551201-[4-(6-Aminopurin-9-yl)phenyl]-3-(4-chloro-3-(trifluoromethyl)phenyl)urea hydrochloride

Product 1

HCID 59725890HCID 59725890, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

In 3 mL of methylene chloride, 110 mg (0.62 mmol) of (2-hydroxyethyl)-methylcarbamic acid tert-butyl ester and 108 μL (0.62 mol) of Hunig's base were dissolved, and 74 mg (0.248 mmol) of triphosgene was added thereto at one time, and the mixture solution was stirred for 15 minutes. To the obtained solution, a solution obtained by dissolving 30 mg (0.062 mmol) of 1-[4-(6-aminopurin-9-yl)phenyl]-3-(4-chloro-3-(trifluoromethyl)phenyl)urea hydrochloride in 3 mL of pyridine was added and the mixture solution was stirred at room temperature for three hours. The reaction solution was concentrated under reduced pressure, and then the residue was partitioned between ethyl acetate and water, and the organic layer was washed with a saturated sodium chloride solution, dried and concentrated. The residue was purified by Megabond Elute Silica Gel (1 g, methanol:ethyl acetate=1:30) to obtain 13 mg (33%) of (9-{4-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-yl]carbamic acid 2-(tert-butoxycarbonylamino)ethyl ester as a white solid.

Workup

  1. customTo the obtained solution, a solution obtained
  2. additionwas added
  3. stirringthe mixture solution was stirred at room temperature for three hours
  4. concentrationThe reaction solution was concentrated under reduced pressure
  5. customthe residue was partitioned between ethyl acetate and water
  6. washthe organic layer was washed with a saturated sodium chloride solution
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by Megabond
  10. washElute Silica Gel (1 g, methanol:ethyl acetate=1:30)

Sources & evidence

ORD record
ord-6c39c8edce274d988a8c6b3359cdd123
Source dataset
uspto-grants-2013_12
Patent number
US08609656B2

Reaction notes

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