Lithium iodide → HCID 25142576, compound

HRID 1677030Notes

Reaction equation

HRID 1677030 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[C:15]([N:17]2[CH2:34][CH2:33][C:20]3[N:21]([CH2:28][C:29]([O:31]C)=[O:30])[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=4[C:19]=3[CH2:18]2)=[O:16])=[O:8])[CH2:5][CH2:4]1)#[N:2].[I-].[Li+]>N1C=CC=CC=1>[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[C:15]([N:17]2[CH2:34][CH2:33][C:20]3[N:21]([CH2:28][C:29]([OH:31])=[O:30])[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=4[C:19]=3[CH2:18]2)=[O:16])=[O:8])[CH2:4][CH2:5]1)#[N:2]

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 25142575HCID 25142575, compound

Product 1

HCID 25142576HCID 25142576, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
150 °C

Procedure

(1R,2R)-N-(1-cyanocyclopropyl)-2-[(5-methoxycarbonylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxamide (150 mg, 0.32 mmol) and lithium iodide (520 mg, 3.89 mmol) were suspended in pyridine (5 mL) in a capped microwave vessel. This was heated in a microwave at 150° C. for one hour (absorbance: N). Pyridine was removed in vacuo and the residue azeotroped once with toluene. It was taken up in 50% brine (20 mL), acidified with acetic acid and partitioned with ethyl acetate (2×80 mL). Combined organics were dried (magnesium sulphate), concentrated in vacuo, azeotroped once with toluene and adsorbed onto silica for purification by flash chromatography (0-20% methanol/DCM). This gave (1R,2R)-N-(1-cyanocyclopropyl)-2-[(5-hydroxycarbonylmethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)carbonyl]cyclohexanecarboxamide as a pale yellow solid (84.0 mg, 59%).

Workup

  1. customPyridine was removed in vacuo
  2. customthe residue azeotroped once with toluene
  3. custompartitioned with ethyl acetate (2×80 mL)
  4. dry with materialCombined organics were dried (magnesium sulphate)
  5. concentrationconcentrated in vacuo
  6. customazeotroped once with toluene
  7. customadsorbed onto silica for purification by flash chromatography (0-20% methanol/DCM)

Sources & evidence

ORD record
ord-4e1112d8b0a44b6d802df57fb90730bf
Source dataset
uspto-grants-2011_08
Patent number
US08008279B2

Reaction notes

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