Amantadine → 5-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid adamantan-2-ylamide

HRID 2264617Notes

Reaction equation

HRID 2264617 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[C:13]12(N)[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2.C([N:26](C(C)C)C(C)C)C.[NH2:33][C:34]1[N:39]=[C:38]([O:40][C:41]2[CH:42]=[C:43]3[C:47](=[CH:48][CH:49]=2)[NH:46][CH2:45][CH2:44]3)[CH:37]=[CH:36][N:35]=1>C(Cl)Cl.C1COCC1.C([O-])(O)=O.[Na+]>[CH:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH:14]1[NH:26][C:5]([N:46]1[C:47]3[C:43](=[CH:42][C:41]([O:40][C:38]4[CH:37]=[CH:36][N:35]=[C:34]([NH2:33])[N:39]=4)=[CH:49][CH:48]=3)[CH2:44][CH2:45]1)=[O:11])[CH2:20]2

Participants

8

Reactant 4

HCID 2130AmantadineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 675302915-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole

Product 1

HCID 675319335-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid adamantan-2-ylamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

130 mg (0.44 mMol) triphosgene are dissolved in 5 ml ice-cooled CH2Cl2. Then a solution of 170 mg (1.12 mMol) adamantan-1-ylamine and 0.5 ml (2.87 mMol) EtN(iPr)2 in 5 ml CH2Cl2 is added during 15 min. After stirring the reaction mixture for further 15 min, a solution of 300 mg (1.33 mMol) 5-(2-amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 26.2) and 0.5 ml (2.87 mMol) EtN(iPr)2 in 5 ml THF is added. After 16 h at rt, the mixture is diluted with 10% NaHCO3 solution and CH2Cl2, the aqueous phase separated off and extracted with CH2Cl2. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; hexane/EtOAc 19:1→3:1) gives the title compound: MS: [M+1]+=406; HPLC: EtRet=3.7.

Workup

  1. waitAfter 16 h at rt
  2. customthe aqueous phase separated off
  3. extractionextracted with CH2Cl2
  4. washThe organic layers are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8151f84192ee4dd895b85264a86c58b3
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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