1,1'-Carbonyldiimidazole → Methyl 2-((S)-(3-chlorophenyl)((R)-4-((2S,3R)-3-hydroxy-4-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-1-(tetrahydro-2H-pyran-4-yl)butan-2-ylcarbamoyl)morpholin-2-yl)methoxy)ethylcarbamate

HRID 253604Notes

Reaction equation

HRID 253604 reaction equation
[NH2:1][C@@H:2]([CH2:17][CH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[C@H:3]([OH:16])[CH2:4][N:5]([CH3:15])[C:6](=[O:14])[O:7][CH2:8][CH2:9][Si:10]([CH3:13])([CH3:12])[CH3:11].C1N=CN([C:29]([N:31]2[CH:35]=N[CH:33]=[CH:32]2)=[O:30])C=1.CCN(C(C)C)C(C)C.[Cl:45][C:46]1[CH:47]=[C:48]([C@@H:52]([C@@H:61]2[O:66]CCNC2)[O:53][CH2:54][CH2:55][NH:56][C:57](=[O:60])[O:58][CH3:59])[CH:49]=[CH:50][CH:51]=1>C(Cl)Cl>[Cl:45][C:46]1[CH:47]=[C:48]([C@@H:52]([C@@H:61]2[O:66][CH2:33][CH2:32][N:31]([C:29](=[O:30])[NH:1][C@H:2]([C@H:3]([OH:16])[CH2:4][N:5]([CH3:15])[C:6]([O:7][CH2:8][CH2:9][Si:10]([CH3:12])([CH3:13])[CH3:11])=[O:14])[CH2:17][CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[CH2:35]2)[O:53][CH2:54][CH2:55][NH:56][C:57](=[O:60])[O:58][CH3:59])[CH:49]=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 57786498methyl 2-((S)-(3-chlorophenyl)((R)-morpholin-2-yl)methoxy)ethylcarbamateHCID 66861533HCID 66861533, compound

Product 1

HCID 66861750Methyl 2-((S)-(3-chlorophenyl)((R)-4-((2S,3R)-3-hydroxy-4-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)-1-(tetrahydro-2H-pyran-4-yl)butan-2-ylcarbamoyl)morpholin-2-yl)methoxy)ethylcarbamateYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(trimethylsilyl)ethyl (2R,3S)-3-amino-2-hydroxy-4-(tetrahydro-2H-pyran-4-yl)butyl(methyl)carbamate (50 mg, 0.12 mmol) and CDI (20 mg, 0.12 mmol) in anhydrous CH2Cl2 (10 mL) cooled in an ice bath, DIEA (78 mg, 0.6 mmol) was added. After addition, the mixture was stirred for 1 h at 0° C. and added to a solution of methyl 2-((S)-(3-chlorophenyl)((R)-morpholin-2-yl)methoxy)ethylcarbamate (59 mg, 0.18 mmol) in anhydrous CH2Cl2 (2 mL). 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 product (30 mg, 36%).

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-fdd5e099df8a47c5997a678b5e700ff0
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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