Sodium Hydroxide → (2S,3R)-2-amino-3-hydroxy-N-{1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-yl}butyramide

HRID 1401782Notes

Reaction equation

HRID 1401782 reaction equation
[CH3:1][C:2]1([CH3:26])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]3[N:15]=[C:16]([N:19]4[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]4)[S:17][CH:18]=3)[CH:5]=[CH:4][C:3]1=2.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC.C(OC([NH:66][C@H:67]([C:71](O)=[O:72])[C@@H:68]([CH3:70])[OH:69])=O)(C)(C)C.[OH-].[Na+]>C1COCC1.CC(=O)OCC>[NH2:66][C@@H:67]([C@H:68]([OH:69])[CH3:70])[C:71]([NH:25][CH:22]1[CH2:23][CH2:24][N:19]([C:16]2[S:17][CH:18]=[C:14]([C:6]3[CH:5]=[CH:4][C:3]4[C:2]([CH3:26])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]=4[CH:7]=3)[N:15]=2)[CH2:20][CH2:21]1)=[O:72]

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724766N-tert-Butoxycarbonyl-L-threonineHCID 27960291-Hydroxybenzotriazole hydrateHCID 53312200HCID 53312200, compound

Product 1

HCID 67323746(2S,3R)-2-amino-3-hydroxy-N-{1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-yl}butyramide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

190 mg (0.47 mmol) of 1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-ylamine were dissolved in 5 ml of THF, and 86 mg (0.56 mmol) of 1-hydroxybenzotriazole hydrate, 239 μl (1.40 mmol) of N-ethyldiisopropylamine, 108 mg (0.56 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 113 mg (0.56 mmol) of N-(tert-butoxycarbonyl)-L-threonine were added. The mixture was stirred at room temperature overnight, dissolved in EA and 1 N NaOH and shaken. The organic phase was washed with water, dried over sodium sulfate, filtered and evaporated. The protecting group was cleaved off as already described using HCl in dioxane. The product was purified by means of preparative HPLC and is in the form of the hydrochloride.

Workup

  1. washThe organic phase was washed with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe product was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-83e3c50a5dbe4f60a639f896333d3818
Source dataset
uspto-grants-2014_12
Patent number
US08907098B2

Reaction notes

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