1,1'-Carbonyldiimidazole → HCID 59201736, compound

HRID 451885Notes

Reaction equation

HRID 451885 reaction equation
[NH2:1][C@@H:2]([C@H:13]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[O:14][Si](C)(C)C)[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.C1N=CN([C:39]([N:41]2[CH:45]=N[CH:43]=[CH:42]2)=[O:40])C=1.[Cl:46][C:47]1[C:52]([F:53])=[CH:51][CH:50]=[CH:49][C:48]=1[C@@:54]([OH:69])([C@@H:63]1CCCN[CH2:64]1)[CH2:55][CH2:56][CH2:57][NH:58][C:59](=[O:62])[O:60][CH3:61]>C(Cl)Cl>[Cl:46][C:47]1[C:52]([F:53])=[CH:51][CH:50]=[CH:49][C:48]=1[C@:54]([C@@H:63]1[CH2:64][CH2:43][CH2:42][N:41]([C:39](=[O:40])[NH:1][C@H:2]([CH2:3][N:4]([CH3:12])[C:5]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:11])[C@H:13]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[OH:14])[CH2:45]1)([OH:69])[CH2:55][CH2:56][CH2:57][NH:58][C:59](=[O:62])[O:60][CH3:61]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 59201347HCID 59201347, compoundHCID 59201749HCID 59201749, compound

Product 1

HCID 59201736HCID 59201736, compoundYield 46.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (2R,3S)-2-amino-3-cyclohexyl-3-(trimethylsilyloxy)propyl(methyl)carbamate (79.8 mg, 0.223 mmol) in anhydrous CH2Cl2 (2 mL) were added DIEA (190 μL, 1.12 mmol) and CDI (36.2 mg, 0.223 mmol). The mixture was stirred at 0° C. for 45 min, and methyl (S)-4-(2-chloro-3-fluorophenyl)-4-hydroxy-4-((R)-piperidin-3-yl)butylcarbamate (80.0 mg, 0.223 mmol) was added in one portion and the mixture was allowed to warm to rt and stirred overnight. The reaction was quenched with water and extracted with CH2Cl2 (3×20 mL). The organic extracts were washed with brine and concentrated to give crude product, which was purified by preparative HPLC to afford methyl (S)-4-(2-chloro-3-fluorophenyl)-4-((R)-1-((1S,2R)-1-cyclohexyl-1-hydroxy-3-(N-methyl-N-(t-butoxycarbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)-4-hydroxybutylcarbamate (70 mg, 46.8%). MS (E/Z): 671 (M+H+).

Workup

  1. temperatureto warm to rt
  2. stirringstirred overnight
  3. customThe reaction was quenched with water
  4. extractionextracted with CH2Cl2 (3×20 mL)
  5. washThe organic extracts were washed with brine
  6. concentrationconcentrated
  7. customto give crude product, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-39a45e5d64d6453285605798c77505da
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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