Triethylamine → N-[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-([{tert-butyl(dimethyl)silyl]oxy}-methyl)cyclopentyl]-6-chloro-5-fluoropyrimidin-4-amine

HRID 1397582Notes

Reaction equation

HRID 1397582 reaction equation
Cl[C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1.[Si:10]([O:17][C@@H:18]1[C@H:22]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:21][C@@H:20]([NH2:32])[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].C(N(CC)CC)C>C(O)C>[Si:10]([O:17][C@@H:18]1[C@H:22]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:26])[CH3:27])[CH2:21][C@@H:20]([NH:32][C:2]2[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=2)[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 112866754,6-Dichloro-5-fluoropyrimidineHCID 59671204(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanamine

Product 1

HCID 86618727N-[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-([{tert-butyl(dimethyl)silyl]oxy}-methyl)cyclopentyl]-6-chloro-5-fluoropyrimidin-4-amineYield 77.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 4,6-dichloro-5-fluoropyrimidine (102 mg, 0.61 mmol), (1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-cyclopentanamine (200 mg, 0.56 mmol), and triethylamine (0.16 mL, 1.11 mmol) in ethanol (2.00 mL) was heated in a sealed tube under microwave irradiation at 140° C. for 1 h. The reaction mixture was concentrated under vacuum, and the residue was purified by flash chromatography (0 to 15% ethyl acetate/hexanes) to afford the title compound (213 mg, 70%) as a light yellow solid. LC/MS: Rt=2.60 min, ES+ 490.5 (AA standard).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was purified by flash chromatography (0 to 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9cfd176c65e440828f04cb2662fc9b13
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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