Sodium Carbonate → 6-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-5-fluoro-N-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]pyrimidin-4-amine

HRID 1677978Notes

Reaction equation

HRID 1677978 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[C:29]([F:30])=[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].[CH3:32][O:33][C@H:34]1[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C@H:35]1[NH2:43].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[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:43][C@@H:35]3[C:36]4[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:42][C@@H:34]3[O:33][CH3:32])[C:29]=2[F:30])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 28109796(1R,2S)-2-Methoxy-2,3-dihydro-1H-inden-1-amineHCID 866187254-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy)-6-chloro-5-fluoropyrimidine

Product 1

HCID 667982116-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-5-fluoro-N-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]pyrimidin-4-amineYield 95.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]-oxy}methyl)cyclopentyl]oxy}-6-chloro-5-fluoropyrimidine (260 mg, 0.53 mmol), (1R,2S)-2-methoxyindan-1-amine (364 mg, 2.12 mmol), and sodium carbonate (224 mg, 2.12 mmol) was weighed into a microwave reaction tube. This mixture was heated in a sealed tube under microwave irradiation at 180° C. for 2 h. The reaction mixture was diluted with DCM (100 mL), and the suspension was filtered. The filtrate was washed with saturated NH4Cl solution (100 mL), and the organic layer was dried over MgSO4. This suspension was filtered, and evaporated under vacuum. The residue was purified via silica gel column chromatography eluting with a gradient of 0 to 10% methanol in DCM to afford the title compound (313 mg, 91%).

Workup

  1. filtrationthe suspension was filtered
  2. washThe filtrate was washed with saturated NH4Cl solution (100 mL)
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationThis suspension was filtered
  5. customevaporated under vacuum
  6. customThe residue was purified via silica gel column chromatography
  7. washeluting with a gradient of 0 to 10% methanol in DCM

Sources & evidence

ORD record
ord-300f35194f7042498988c8a304ca019a
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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