1,1'-Thiocarbonyldiimidazole → methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(tert-butoxycarbonyl)amino)propan-2-ylcarbamothioyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 451902Notes

Reaction equation

HRID 451902 reaction equation
[NH2:1][C@@H:2]([CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].CCN(C(C)C)C(C)C.[Cl:29][C:30]1[CH:31]=[C:32]([C@@H:36]([C@@H:45]2[CH2:50][CH2:49][CH2:48][NH:47][CH2:46]2)[O:37][CH2:38][CH2:39][NH:40][C:41](=[O:44])[O:42][CH3:43])[CH:33]=[CH:34][CH:35]=1.N1([C:56](N2C=CN=C2)=[S:57])C=CN=C1>C(OCC)(=O)C>[Cl:29][C:30]1[CH:31]=[C:32]([C@@H:36]([C@@H:45]2[CH2:50][CH2:49][CH2:48][N:47]([C:56](=[S:57])[NH:1][C@H:2]([CH2:3][N:4]([CH3:12])[C:5]([O:6][C:7]([CH3:9])([CH3:10])[CH3:8])=[O:11])[CH2:13][CH:14]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]3)[CH2:46]2)[O:37][CH2:38][CH2:39][NH:40][C:41](=[O:44])[O:42][CH3:43])[CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 802641,1'-ThiocarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 59201313tert-butyl (S)-2-amino-3-cyclohexylpropylmethylcarbamateHCID 59598478Carbamic acid,N-[2-[(R)-(3-chlorophenyl)(3R)-3-piperidinylmethoxy]ethyl]-,methyl ester

Product 1

HCID 59201614methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(tert-butoxycarbonyl)amino)propan-2-ylcarbamothioyl)piperidin-3-yl)methoxy)ethylcarbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (S)-tert-butyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (326 mg, 1 mmol), DIEA (258 mg, 2 mmol) and methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate (270 mg, 1 mmol) in ethyl acetate (6 mL) was added dropwise a solution of di-imidazol-1-yl-methanethione (194 mg, 1 mmol) in ethyl acetate (4 mL) at 0-5° C. After addition, the mixture was allowed to warm to room temperature for 3-4 h, the mixture was washed with water (20 mL) and brine (20 ml), the organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the residue, which was purified by preparative TLC to afford methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(tert-butoxycarbonyl)amino)propan-2-ylcarbamothioyl)piperidin-3-yl)methoxy)ethylcarbamate. MS ESI +ve m/z 638 (M+H).

Workup

  1. additionAfter addition
  2. washthe mixture was washed with water (20 mL) and brine (20 ml)
  3. dry with materialthe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the residue, which
  7. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-25b9da80b01e4a1a89e32958d4aec5fd
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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