Diisopropylethylamine → HCID 16752762, compound

HRID 2266295Notes

Reaction equation

HRID 2266295 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([C@@H:17]2[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]2)[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:16])[O:14][CH3:15])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH2:32]([NH:36][C:37](=[O:69])[CH2:38][C@H:39]([O:61][Si](C(C)(C)C)(C)C)[C@@H:40]([NH:48][C:49](=O)[O:50]C1C=CC([N+]([O-])=O)=CC=1)[CH2:41][CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[CH2:33][CH2:34][CH3:35]>C(Cl)Cl.CCOCC>[CH2:32]([NH:36][C:37](=[O:69])[CH2:38][C@H:39]([OH:61])[C@@H:40]([NH:48][C:49]([N:19]1[CH2:20][CH2:21][CH2:22][C@@H:17]([C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:16])[O:14][CH3:15])[CH2:18]1)=[O:50])[CH2:41][CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[CH2:33][CH2:34][CH3:35]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57918966HCID 57918966, compoundHCID 59598478Carbamic acid,N-[2-[(R)-(3-chlorophenyl)(3R)-3-piperidinylmethoxy]ethyl]-,methyl ester

Product 1

HCID 16752762HCID 16752762, compoundYield 68.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate (40 mg, 0.12 mmol) and DIEA (0.10 mL, 0.55 mmol) in CH2Cl2 (1 mL) was added to 4-nitrophenyl (2S,3S)-5-(butylamino)-3-(tert-butyldimethylsilyloxy)-1-cyclohexyl-5-oxopentan-2-ylcarbamate (39 mg, 0.07 mmol). The mixture was stirred at rt for 3 h, diluted with ether (100 mL), washed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL) and dried over MgSO4. Removal of the solvent left an oil (43 mg) which was dissolved in MeCN (2 mL) and treated with Et4N+F− (25 mg, 0.18 mmol). The solution was stirred at rt for 3 h and submitted directly to preparative HPLC to afford Methyl 2-((R)-((R)-1-((2S,3S)-5-(butylamino)-1-cyclohexyl-3-hydroxy-5-oxopentan-2-ylcarbamoyl)piperidin-3-yl)(3-chlorophenyl)methoxy)ethylcarbamate (30 mg, 38%) as an oil. 1H NMR (CD3OD) 0.92 (t, 3H), 1.0-1.9 (22H), 2.26 (m, 1H), 2.35 (m, 1H), 2.92 (m, 2H), 3.17 (m, 2H), 3.23 (m, 2H), 3.30 (2H), 3.61 (s, 3H), 3.80 (br d, 1H), 3.88 (br d, 1H), 3.94 (m, 1H), 4.03 (d, 1H), 4.15 (br d, 1H), 7.21 (d, 1H), 7.34 (3H); LC-MS (16 min) tR=9.89 min, m/z=623. It is noted that although the compound described in this example was the only compound prepared, the other compounds of the invention described herein could be prepared in accordance with the methods taught herein.

Workup

  1. washwashed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL)
  2. dry with materialdried over MgSO4
  3. customRemoval of the solvent
  4. waitleft an oil (43 mg) which
  5. dissolutionwas dissolved in MeCN (2 mL)
  6. additiontreated with Et4N+F− (25 mg, 0.18 mmol)
  7. stirringThe solution was stirred at rt for 3 h

Sources & evidence

ORD record
ord-59e4533e30fe4b13950fa830581a64ab
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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