Triphenylphosphine → N-[4-(2-Amino-8-(3-(tert-butoxycarbonylamino)-propyl)-9H-purin-6-yloxymethyl)-benzyl]-2,2,2-trifluoro-acetamide

HRID 1695092Notes

Reaction equation

HRID 1695092 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])=[CH:12][CH:11]=2)[C:5]([N:24]=O)=[C:4]([NH:26][C:27](=O)[CH2:28][CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC1C=CC=CC=1C>[NH2:1][C:2]1[N:3]=[C:4]2[C:5]([N:24]=[C:27]([CH2:28][CH2:29][CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:36])[CH3:37])=[O:33])[NH:26]2)=[C:6]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][NH:17][C:18](=[O:23])[C:19]([F:21])([F:20])[F:22])=[CH:14][CH:15]=2)[N:7]=1

Participants

4

Reactant 2

HCID 11776TriphenylphosphineHCID 866156122-Amino-6-(4-(tert-butoxycarbonylamino)-butanoylamino)-5-nitroso-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidine

Product 1

HCID 178453369N-[4-(2-Amino-8-(3-(tert-butoxycarbonylamino)-propyl)-9H-purin-6-yloxymethyl)-benzyl]-2,2,2-trifluoro-acetamideYield 107%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

Nitroso-pyrimidine 39 (Example 22, 1.84 g, 3.3 mmol) and triphenylphosphine (1.89 g, 7 mmol) in 20 mL o-xylene are heated to reflux for 10 h. After cooling to room temperature the solvent is removed in vacuo and the remaining residue redissolved in ethyl acetate. The residue is adsorbed on SiO2 and purified by flash column chromatography (ethyl acetate/ethanol 1:0 to 10:1) to yield the title compound as a colorless solid (1.04 g, 3.53 mmol, 50.4%). 1H-NMR (400 MHz, DMSO-d6): δ=7.46 (d, J=8.1, 2H, ArH), 7.28 (d, J=8.1, 2H, ArH), 6.85 (t, J=5.3, 1H, CONH), 6.41 (s, 2H, NH2), 5.41 (s, 2H, OCH2), 4.38 (s, 2H, CH2), 2.93 (q, J=6.5, 2H, CH2), 2.60 (t, J=7.1, 2H, CH2), 1.76 (qt, J=7.1; 2H, CH2), 1.35 (s, 9H, (CH3)3) ppm. MS (ESI) m/z 524.3 [M+H]+.

Workup

  1. temperatureto reflux for 10 h
  2. customis removed in vacuo
  3. dissolutionthe remaining residue redissolved in ethyl acetate
  4. custompurified by flash column chromatography (ethyl acetate/ethanol 1:0 to 10:1)

Sources & evidence

ORD record
ord-f9da7f9c7e5c44768ab5632fb2d20ffe
Source dataset
uspto-grants-2012_04
Patent number
US08163479B2

Reaction notes

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