Diisopropylethylamine → (S)-1-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

HRID 336217Notes

Reaction equation

HRID 336217 reaction equation
Cl.[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([C@@H:14]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][NH:15]2)=[O:13])[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.[O:30]=[S:31]1(=[O:40])[CH2:36][CH2:35][N:34]([C:37](Cl)=[O:38])[CH2:33][CH2:32]1>CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([C@@H:14]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]2[C:37]([N:34]2[CH2:35][CH2:36][S:31](=[O:40])(=[O:30])[CH2:32][CH2:33]2)=[O:38])=[O:13])[CH:7]=1)([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 216949071,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl chlorideHCID 86660403(S)-Perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide hydrochloride

Product 1

HCID 58564080(S)-1-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-perhydro-azepine-2-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide hydrochloride (0.30 g, 1.13 mmol), DIPEA (0.32 g, 2.48 mmol) and DMAP (16.0 mg, 0.13 mmol) is stirred at room temperature for 15 minutes. 1,1-Dioxo-1λ6-thiomorpholine-4-carbonyl chloride (0.27 g, 1.35 mmol) (prepared according to method M step 1) is added drop wise at 0° C. to the reaction mixture that is slowly warmed up to room temperature and stirred for 14 hours. The reaction mixture is diluted with EtOAc, washed with water and brine. After drying the organic phase over anhydrous Na2SO4, removal of the solvent under reduced pressured affords the crude product that is purified by prep TLC to afford the title product; m/z 427 [M+H+].

Workup

  1. washwashed with water and brine
  2. customAfter drying the organic phase
  3. customover anhydrous Na2SO4, removal of the solvent
  4. customaffords the crude product that
  5. customis purified by prep TLC

Sources & evidence

ORD record
ord-70be7240cd7341b8bc9b56d410acef49
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

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