Diisopropylethylamine → [1-(9-{4-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-ylcarbonyl)-3-methyl-butyl]carbamic acid tert-butyl ester

HRID 1912813Notes

Reaction equation

HRID 1912813 reaction equation
Cl.N[C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=2)=[O:20])=[CH:14][CH:13]=1.[C:33]([O:37][C:38]([NH:40][C@H:41]([C:46](O)=[O:47])[CH2:42][CH:43]([CH3:45])[CH3:44])=[O:39])([CH3:36])([CH3:35])[CH3:34].F[P-](F)(F)(F)(F)F.N1C2C=CC=C(O[P+](N3CCCC3)(N3CCCC3)N3CCCC3)C=2N=N1.CCN(C(C)C)C(C)C>O1CCCC1>[C:33]([O:37][C:38](=[O:39])[NH:40][CH:41]([C:46]([C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=2)=[O:20])=[CH:14][CH:13]=1)=[O:47])[CH2:42][CH:43]([CH3:44])[CH3:45])([CH3:34])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 231551201-[4-(6-Aminopurin-9-yl)phenyl]-3-(4-chloro-3-(trifluoromethyl)phenyl)urea hydrochlorideHCID 178506432HCID 178506432, compound

Product 1

HCID 69318573[1-(9-{4-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-ylcarbonyl)-3-methyl-butyl]carbamic acid tert-butyl esterYield 79.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 15 ml of tetrahydrofuran, 300 mg (0.620 mmol) of 1-[4-(6-aminopurin-9-yl)phenyl]-3-(4-chloro-3-(trifluoromethyl)phenyl)urea hydrochloride was dissolved, and 771 mg (3.10 mmol) of tert-butoxycarbonyl-L-leucine, 1.60 g (3.10 mmol) of (benzotriazolyloxy)tripyrrolidino-phosphonium hexa-fluorophosphate (PyBOP) and 0.54 mL (3.10 mmol) of Hunig's base were added thereto and the mixture solution was stirred at room temperature for three days. The reaction solution was concentrated under reduced pressure, and then the residue was partitioned between ethyl acetate and water. The organic phase was washed with a saturated sodium chloride solution, dried, and then concentrated under reduced pressure. The residue was purified by Megabond Elute Silica Gel (10 g, ethyl acetate), to obtain 320 mg (78%) of [1-(9-{4-[3-(4-chloro-3-(trifluoromethyl)phenyl)ureido]phenyl}-9H-purin-6-ylcarbonyl)-3-methyl-butyl]carbamic acid tert-butyl ester as a white solid.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and water
  3. washThe organic phase was washed with a saturated sodium chloride solution
  4. customdried
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by Megabond
  7. washElute Silica Gel (10 g, ethyl acetate)

Sources & evidence

ORD record
ord-a5b75c64720a483891def1d2a8d0033c
Source dataset
uspto-grants-2013_12
Patent number
US08609656B2

Reaction notes

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