Acetic Acid → (1R,2S,3R)-3-{1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-ylamino}cyclopentane-1,2-diol

HRID 1401857Notes

Reaction equation

HRID 1401857 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][C@@H:5]([OH:8])[C@H:4]1[OH:9].CCN(C(C)C)C(C)C.[CH3:19][C:20]1([CH3:44])[CH2:29][CH2:28][C:27]([CH3:31])([CH3:30])[C:26]2[CH:25]=[C:24]([C:32]3[N:33]=[C:34]([N:37]4[CH2:42][CH2:41][C:40](=O)[CH2:39][CH2:38]4)[S:35][CH:36]=3)[CH:23]=[CH:22][C:21]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>[CH3:19][C:20]1([CH3:44])[CH2:29][CH2:28][C:27]([CH3:30])([CH3:31])[C:26]2[CH:25]=[C:24]([C:32]3[N:33]=[C:34]([N:37]4[CH2:42][CH2:41][CH:40]([NH:2][C@@H:3]5[CH2:7][CH2:6][C@@H:5]([OH:8])[C@H:4]5[OH:9])[CH2:39][CH2:38]4)[S:35][CH:36]=3)[CH:23]=[CH:22][C:21]1=2

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 13497975(1R,2S,3R)-3-aminocyclopentane-1,2-diol hydrochlorideHCID 673225751-[4-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-one

Product 1

HCID 67325209(1R,2S,3R)-3-{1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-ylamino}cyclopentane-1,2-diol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

24 mg (0.16 mmol) of (1R,2S,3R)-3-aminocyclopentane-1,2-diol hydrochloride are dissolved in 1 ml of THF and 2 ml of DMF, and 27 μl (0.16 mmol) of DIPEA are added. 60 mg (0.16 mmol) of 1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-one are added. The mixture is stirred at room temperature for 30 min, 18 μl (0.32 mmol) of glacial acetic acid are added, and the mixture is stirred for a further 10 min. 70 mg (0.32 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-61cc98d5346442cd9b79d5e2369b4404
Source dataset
uspto-grants-2014_12
Patent number
US08907098B2

Reaction notes

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