1-Butanol → 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-N-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]pyrimidin-4-amine

HRID 1397546Notes

Reaction equation

HRID 1397546 reaction equation
[Si:1]([O:8][C@@H:9]1[C@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:12][C@@H:11]([O:23][C:24]2[CH:29]=[C:28](Cl)[N:27]=[CH:26][N:25]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:31][O:32][C@H:33]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C@H:34]1[NH2:42].C(N(CC)CC)C.C(O)CCC>>[Si:1]([O:8][C@@H:9]1[C@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:12][C@@H:11]([O:23][C:24]2[N:25]=[CH:26][N:27]=[C:28]([NH:42][C@@H:34]3[C:35]4[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH2:41][C@@H:33]3[O:32][CH3:31])[CH:29]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 2631-ButanolHCID 8471TriethylamineHCID 28109796(1R,2S)-2-Methoxy-2,3-dihydro-1H-inden-1-amineHCID 596712514-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine

Product 1

HCID 667979016-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-N-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]pyrimidin-4-amineYield 79%

Procedure

A mixture of 4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine (260.0 mg, 0.0005494 mol), (1R,2S)-2-methoxyindan-1-amine (0.359 g, 0.00220 mol) and triethylamine (115 μL, 0.000824 mol) in 1-butanol (0.97 mL, 0.011 mol) was subjected to microwave irradiation (300 watts, 200° C.) for 30 minutes. The resulting dark brown mixture was filtered and concentrated. The residue was purified by flash chromatography (0 to 15% EtOAc/hexanes) to give 0.26 g (79%) of the title compound. LC/MS: Rt=3.42 min, ES+ 600 (AA standard).

Workup

  1. customwas subjected to microwave irradiation (300 watts, 200° C.) for 30 minutes
  2. filtrationThe resulting dark brown mixture was filtered
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography (0 to 15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-288d06ab95174fb99c125982b1d94b3d
Source dataset
uspto-grants-2014_12
Patent number
US08901136B2

Reaction notes

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