Ammonia → 9-(4-{[(5-Cyanopyridin-2-yl)oxy]methyl}-3,3-dimethyl-2-oxopyrrolidin-1-yl)bicyclo[3.3.1]nonane-3-carboxamide

HRID 2115622Notes

Reaction equation

HRID 2115622 reaction equation
Cl.C([N:4]=C=NCCCN(C)C)C.[C:13]([C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH:23]2[CH2:27][N:26]([CH:28]3[CH:33]4[CH2:34][CH2:35][CH2:36][CH:29]3[CH2:30][CH:31]([C:37]([OH:39])=O)[CH2:32]4)[C:25](=[O:40])[C:24]2([CH3:42])[CH3:41])=[N:19][CH:20]=1)#[N:14].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.N>ClCCl>[C:13]([C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH:23]2[CH2:27][N:26]([CH:28]3[CH:29]4[CH2:36][CH2:35][CH2:34][CH:33]3[CH2:32][CH:31]([C:37]([NH2:4])=[O:39])[CH2:30]4)[C:25](=[O:40])[C:24]2([CH3:41])[CH3:42])=[N:19][CH:20]=1)#[N:14]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666569469-[4-(5-Cyano-pyridin-2-yloxymethyl)-3,3-dimethyl-2-oxo-pyrrolidin-1-yl]-bicyclo[3.3.1]nonane-3-carboxylic acid

Product 1

HCID 248899069-(4-{[(5-Cyanopyridin-2-yl)oxy]methyl}-3,3-dimethyl-2-oxopyrrolidin-1-yl)bicyclo[3.3.1]nonane-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (0.35 g, 1.81 mmol) was added in one portion to a stirred solution of the product of Example 7F (0.50 g, 1.21 mmol), 1-hydroxybenzotriazole hydrate (0.32 g, 2.42 mmol), and diisopropylethyl amine (0.63 mL, 3.63 mmol) in dry dichloromethane (7 mL). The resulting solution was stirred at room temperature for two hours before ammonia solution (2.5 mL, 2 M in isopropanol, 4.8 mmol) was added. The resulting white suspension was stirred for one hour before it was diluted with dichloromethane (50 mL) and washed with 20% NaHSO4 solution, 1 M NaOH, water, and brine. The solution was then dried (Na2SO4), filtered, and evaporated. The residue was purified over silica gel using 1-10% methanol in dichloromethane to give the title product as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 1.08 (s, 3H) 1.24 (s, 3H) 1.32-1.51 (m, 2H) 1.50-2.14 (m, 8H) 2.17-2.59 (m, 3H) 2.57-2.75 (m, 1H) 3.27-3.45 (m, 1H) 3.64-3.83 (m, J=9.66, 7.63 Hz, 1H) 3.92 (s, 1H) 4.31-4.45 (m, 1H) 4.46-4.61 (m, 1H) 5.38 (s, 1H) 5.54 (s, 1H) 6.83 (dd, J=8.82, 0.68 Hz, 1H) 7.81 (dd, J=8.82, 2.37 Hz, 1H) 8.48 (dd, J=2.37, 0.68 Hz, 1H).). MS (ESI+) m/z 411.2 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with 20% NaHSO4 solution, 1 M NaOH, water, and brine
  3. dry with materialThe solution was then dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified over silica gel using 1-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-ba1f2adcf3bf43ada925237245459318
Source dataset
uspto-grants-2008_10
Patent number
US07435833B2

Reaction notes

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