Sodium Bicarbonate → {(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(4-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-1,3,5-triazin-2-yl)amino]cyclopentyl}methanol

HRID 447615Notes

Reaction equation

HRID 447615 reaction equation
C(OC[C@H:10]1[C@@H:14]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:13][C@H:12]([NH:23][CH:24]2[N:29]([C@@H:30]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][C@@H:31]3[O:39][CH3:40])[C:28]([NH2:41])=[N:27][C:26](Cl)=[N:25]2)[CH2:11]1)C1C=CC=CC=1.[C:43]([O-:46])(O)=O.[Na+]>CO.C(Cl)Cl.[Pd]>[Si:16]([O:15][C@H:14]1[CH2:13][C@H:12]([NH:23][C:24]2[N:41]=[C:28]([NH:29][C@@H:30]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][C@@H:31]3[O:39][CH3:40])[N:27]=[CH:26][N:25]=2)[CH2:11][C@H:10]1[CH2:43][OH:46])([C:19]([CH3:21])([CH3:20])[CH3:22])([CH3:18])[CH3:17]

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 66798074N-((1R,3S,4S)-3-[(benzyloxy)methyl]-4-{[tert-butyl(dimethyl)-silyl]oxy}cyclopentyl)-6-chloro-M-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazine-2,4-diamine

Product 1

HCID 66798103{(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(4-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-1,3,5-triazin-2-yl)amino]cyclopentyl}methanolYield 57%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of N-((1R,3S,4S)-3-[(benzyloxy)methyl]-4-{[tert-butyl(dimethyl)-silyl]oxy}cyclopentyl)-6-chloro-M-[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1,3,5-triazine-2,4-diamine (250 mg, 0.00041 mol) and 10% Pd/C (44 mg, 0.000041 mol) in methanol (1.61 mL) was stirred under an atmosphere of hydrogen for 2 days. The reaction was purged with nitrogen and filtered through celite with EtOAc. The filtrate was concentrated to obtain a yellow oil. The oil was taken up in CH2Cl2 and saturated NaHCO3. The layers were separated and the aqueous was extracted with CH2Cl2 (1×). The combined organics were dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) to obtain 114 mg (57%) of the title compound. LC/MS: Rt=1.68 min, ES+ 486 (FA standard).

Workup

  1. customThe reaction was purged with nitrogen
  2. filtrationfiltered through celite with EtOAc
  3. concentrationThe filtrate was concentrated
  4. customto obtain a yellow oil
  5. customThe layers were separated
  6. extractionthe aqueous was extracted with CH2Cl2 (1×)
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b265e3e4f292492d80d723615a47d413
Source dataset
uspto-grants-2013_07
Patent number
US08481550B2

Reaction notes

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