Methyl iodide → CERATAMINE A

HRID 1928516Notes

Reaction equation

HRID 1928516 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][NH:12][C:13]1[NH:23][C:22]2[C:15](=[C:16]([CH2:24][C:25]3[CH:30]=[C:29]([Br:31])[C:28]([O:32][CH3:33])=[C:27]([Br:34])[CH:26]=3)[C:17]([N:19]=[CH:20][CH:21]=2)=[O:18])[N:14]=1.I[CH3:36]>CN(C=O)C.C1COCC1>[CH3:11][NH:12][C:13]1[N:23]=[C:22]2[C:15](=[C:16]([CH2:24][C:25]3[CH:26]=[C:27]([Br:34])[C:28]([O:32][CH3:33])=[C:29]([Br:31])[CH:30]=3)[C:17]([N:19]([CH3:36])[CH:20]=[CH:21]2)=[O:18])[N:14]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11201846Ceratamine B

Product 1

HCID 11488186CERATAMINE AYield 43.6%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

Sodium bis(trimethylsilyl)amide (1 M in THF, 24 μL, 0.0240 mmol) was added dropwise to a solution of ceratamine B from Example 12 (formula (IIIB); R1=methyl) (12.1 mg, 0.0266 mmol) in DMF:THF (1:1, 0.27 mL) at 0° C. The reaction mixture was cooled to −78° C. and iodomethane (2.1 μL, 0.0346 mmol) was added dropwise followed by warming to −10° C. The reaction was quenched by the addition H2O (2 mL), and was extracted with EtOAc (6×5 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo to afford crude ceratamine A (formula (IIIA); R1=methyl). Purification by flash chromatography (C-18 reverse-phase silica, 70% MeOH:H2O) yielded pure ceratamine A (formula (IIIA); R1=methyl) (5.4 mg, 0.0116 mmol, 43%) as a yellow solid. The major tautomer was characterized: 1H NMR (400 MHz, DMSO) δ 8.68 (m, NH), 7.74 (d, J=9.9 Hz, 1H), 7.66 (s, 2H), 6.42 (d, J=9.9 Hz, 1H), 4.23 (s, 2H), 3.72 (s, 3H), 3.55 (s, 3H), 3.07 (d, J=4.9 Hz, 3H); 13C NMR (100 MHz, DMSO) δ 175.6, 169.7, 164.1, 160.5, 151.4, 142.9, 140.2, 133.1, 121.3, 116.6, 100.4, 60.3, 43.7, 35.0, 29.2; HRMS (ESI) m/z calcd for C17H17Br2N4O2: 466.9713. found: 466.9701. These data from synthetic ceratamine A are consistent with data reported for natural products.

Workup

  1. temperatureby warming to −10° C
  2. customThe reaction was quenched by the addition H2O (2 mL)
  3. extractionwas extracted with EtOAc (6×5 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto afford crude ceratamine A (formula (IIIA); R1=methyl)
  7. customPurification by flash chromatography (C-18 reverse-phase silica, 70% MeOH:H2O)

Sources & evidence

ORD record
ord-bc402d8c6b3f499c95744478e9bd7b51
Source dataset
uspto-grants-2012_05
Patent number
US08183365B2

Reaction notes

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