1,1'-Carbonyldiimidazole → HCID 86629528, compound

HRID 1711166Notes

Reaction equation

HRID 1711166 reaction equation
Cl.[CH3:2][O:3][NH2:4].C1N=CN([C:10](N2C=NC=C2)=[O:11])C=1.CCN(C(C)C)C(C)C.[C:26]([O:30][C:31](=[O:52])[NH:32][CH2:33][CH2:34][C@H:35]([N:37]1[CH2:42][CH2:41][CH:40]([NH:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[CH:46]=2)[CH2:39][CH2:38]1)[CH3:36])([CH3:29])([CH3:28])[CH3:27]>CC#N>[C:26]([O:30][C:31](=[O:52])[NH:32][CH2:33][CH2:34][C@H:35]([N:37]1[CH2:38][CH2:39][CH:40]([N:43]([CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[CH:46]=2)[C:10]([NH:4][O:3][CH3:2])=[O:11])[CH2:41][CH2:42]1)[CH3:36])([CH3:27])([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 68774079HCID 68774079, compound

Product 1

HCID 86629528HCID 86629528, compoundYield 60.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of methoxyamine HCl (0.25 g, 3.04 mmol) in CH3CN (5 ml) was added CDI (0.49 g, 3.04 mmol) and DIPEA (0.53 mL, 3.04 mmol). The mixture was stirred at 60° C. for 2 h, then a solution of {(R)-3-[4-(3-chloro-benzylamino)-piperidin-1-yl]-butyl}-carbamic acid tert-butyl ester (305 mg, 0.76 mmol) in CH3CN (5 ml) was added to the previous mixture. After stirring at 60° C. overnight, the mixture was concentrated in vacuo and diluted with CH2Cl2 (15 ml) and saturated NaHCO3 (20 ml). The aqueous layer was extracted with CH2Cl2 (3×10 ml), then the combined organic extracts were dried over Na2SO4 and concentrated. The crude product contained 2:1 product/starting material in the 1H NMR and was purified by flash chromatography (CH2Cl2, 7% MeOH, 1% NH4OH) to afford ((R)-3-{4-[1-(3-chloro-benzyl)-3-methoxy-ureido]-piperidin-1-yl}-butyl)-carbamic acid tert-butyl ester as a yellow oil (215 mg, 60%). 1H NMR (CDCl3) δ 0.92-0.95 (d, 3H, J=9 Hz), 1.37 (s, 9H), 1.47-1.82 (m, 6H), 2.13-2.25 (m, 1H), 2.48-2.57 (m, 1H), 2.63-2.89 (m, 3H), 2.99-3.09 (m, 1H), 3.23-3.38 (m, 1H), 3.65 (s, 3H), 4.14-4.26 (m, 1H), 4.31 (s, 2H), 5.90 (br s, 1H), 6.97 (s, 1H), 7.06-7.17 (m, 1H), 7.22 (s, 1H), 7.29 (s, 1H), 7.69 (s, 1H).

Workup

  1. stirringAfter stirring at 60° C. overnight
  2. concentrationthe mixture was concentrated in vacuo
  3. additiondiluted with CH2Cl2 (15 ml) and saturated NaHCO3 (20 ml)
  4. extractionThe aqueous layer was extracted with CH2Cl2 (3×10 ml)
  5. dry with materialthe combined organic extracts were dried over Na2SO4
  6. concentrationconcentrated
  7. customwas purified by flash chromatography (CH2Cl2, 7% MeOH, 1% NH4OH)

Sources & evidence

ORD record
ord-286cfcd5c5db463ea1b7a6b8346fb3c1
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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