Acetic Acid → (1R,2S,3R)-3-[6'-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3,4,5,6-tetrahydro-2H-1,2'-bipyridinyl-4-ylamino]cyclopentane-1,2-diol

HRID 2175099Notes

Reaction equation

HRID 2175099 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][C@@H:4]([OH:7])[C@H:3]1[OH:8].CCN(C(C)C)C(C)C.[CH3:18][C:19]1([CH3:44])[CH2:28][CH2:27][C:26]([CH3:30])([CH3:29])[C:25]2[CH:24]=[C:23]([C:31]3[N:36]=[C:35]([N:37]4[CH2:42][CH2:41][C:40](=O)[CH2:39][CH2:38]4)[CH:34]=[CH:33][CH:32]=3)[CH:22]=[CH:21][C:20]1=2.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C1COCC1.CN(C=O)C>[CH3:18][C:19]1([CH3:44])[CH2:28][CH2:27][C:26]([CH3:29])([CH3:30])[C:25]2[CH:24]=[C:23]([C:31]3[N:36]=[C:35]([N:37]4[CH2:42][CH2:41][CH:40]([NH:1][C@@H:2]5[CH2:6][CH2:5][C@@H:4]([OH:7])[C@H:3]5[OH:8])[CH2:39][CH2:38]4)[CH:34]=[CH:33][CH:32]=3)[CH:22]=[CH:21][C:20]1=2

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 13497976(1R,2S,3R)-3-aminocyclopentane-1,2-diolHCID 672484016'-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2,3,5,6-tetrahydro-1,2'-bipyridinyl-4-one

Product 1

HCID 68380456(1R,2S,3R)-3-[6'-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3,4,5,6-tetrahydro-2H-1,2'-bipyridinyl-4-ylamino]cyclopentane-1,2-diol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

31 mg (0.199 mmol) of (1R,2S,3R)-3-aminocyclopentane-1,2-diol are dissolved in 3.5 ml of THF and 2 ml of DMF, and 33.8 μl of DIPEA are added. 80 mg (0.199 mmol) of 6′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2,3,5,6-tetrahydro-1,2′-bipyridinyl-4-one are added. The mixture is stirred at room temperature for 30 min, 23 μl (0.398 mmol) of glacial acetic acid are added, and the mixture is stirred for a further 10 min. 89 mg (0.398 mmol) of sodium triacetoxyborohydride are subsequently added. The reaction mixture is stirred at room temperature overnight, a concentrated sodium hydrogencarbonate solution is added, and the mixture is extracted twice with EA. The organic phase is dried over sodium sulfate, filtered and evaporated. The residue is purified by means of preparative HPLC. The product is in the form of the hydrochloride.

Workup

  1. stirringthe mixture is stirred for a further 10 min
  2. stirringThe reaction mixture is stirred at room temperature overnight
  3. extractionthe mixture is extracted twice with EA
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by means of preparative HPLC

Sources & evidence

ORD record
ord-c23db8b055744c7585ec7a32f5ebaec0
Source dataset
uspto-grants-2015_06
Patent number
US09062015B2

Reaction notes

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