1,1'-Carbonyldiimidazole → methyl 2-((R)-((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(t-butoxycarbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)(3-fluorophenyl)methoxy)ethylcarbamate

HRID 451887Notes

Reaction equation

HRID 451887 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].C1N=CN([C:25]([N:27]2[CH:31]=N[CH:29]=[CH:28]2)=[O:26])C=1.CCN(C(C)C)C(C)C.[F:41][C:42]1[CH:43]=[C:44]([C@@H:48]([C@@H:57]2CCCN[CH2:58]2)[O:49][CH2:50][CH2:51][NH:52][C:53](=[O:56])[O:54][CH3:55])[CH:45]=[CH:46][CH:47]=1>C(Cl)Cl>[CH:14]1([CH2:13][C@H:2]([NH:1][C:25]([N:27]2[CH2:28][CH2:29][CH2:58][C@@H:57]([C@H:48]([C:44]3[CH:45]=[CH:46][CH:47]=[C:42]([F:41])[CH:43]=3)[O:49][CH2:50][CH2:51][NH:52][C:53](=[O:56])[O:54][CH3:55])[CH2:31]2)=[O:26])[CH2:3][N:4]([CH3:12])[C:5]([O:6][C:7]([CH3:9])([CH3:10])[CH3:8])=[O:11])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 58017404methyl 2-((R)-(3-fluorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamateHCID 59201313tert-butyl (S)-2-amino-3-cyclohexylpropylmethylcarbamate

Product 1

HCID 59201565methyl 2-((R)-((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(t-butoxycarbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)(3-fluorophenyl)methoxy)ethylcarbamateYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (S)-2-amino-3-cyclohexylpropylmethylcarbamate (65 mg, 0.24 mmol) and CDI (40 mg, 0.24 mmol) in anhydrous CH2Cl2 (5 mL) cooled in an ice bath was added DIEA (104 mg, 0.81 mmol). After addition, the mixture was stirred for 1 h at 0° C., a solution of methyl 2-((R)-(3-fluorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate (50 mg, 0.16 mmol) in anhydrous CH2Cl2 (5 mL) was added dropwise. The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was complete, the solvent was removed in vacuo. The product was purified by preparative tlc to afford the desired isomer of methyl 2-((R)—((R)-1-((S)-1-cyclohexyl-3-(N-methyl-N-(t-butoxycarbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)(3-fluorophenyl)methoxy)ethylcarbamate (50 mg, 52% yield). MS (E/Z): 607 (M+H+).

Workup

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by preparative tlc

Sources & evidence

ORD record
ord-d38e3a2d84214c688a70413a2a4bc0fe
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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