Sodium Iodide → HCID 70984361, compound

HRID 403346Notes

Reaction equation

HRID 403346 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:19][CH2:18][C@@H:17]([OH:20])[C:12]2=[N:13][CH:14]=[CH:15][N:16]=[C:11]2[C@H:10]1[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].N1([C:34]([N:36]2[CH2:41][CH2:40][CH:39]([N:42]3[C:50]4[C:45](=[N:46][CH:47]=[CH:48][CH:49]=4)[NH:44][C:43]3=[O:51])[CH2:38][CH2:37]2)=[O:35])C=CN=C1.[Na+].[I-]>CN(C)C=O>[O:51]=[C:43]1[NH:44][C:45]2=[N:46][CH:47]=[CH:48][CH:49]=[C:50]2[N:42]1[CH:39]1[CH2:38][CH2:37][N:36]([C:34]([O:20][C@H:17]2[C:12]3[C:11](=[N:16][CH:15]=[CH:14][N:13]=3)[C@@H:10]([NH:21][C:22]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:28])[C@H:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])[CH2:19][CH2:18]2)=[O:35])[CH2:41][CH2:40]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 584679821-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-oneHCID 71006842HCID 71006842, compound

Product 1

HCID 70984361HCID 70984361, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 100 mL round-bottomed flask was dissolved tert-butyl (5S,6S,9R)-6-(2,3-difluorophenyl)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyrazin-5-ylcarbamate (40 mg, 0.102 mmol) (azeotroped with dry benzene) and 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (41.5 mg, 0.133 mmol) in dimethylformamide (1 mL) to give a colorless suspension under nitrogen. After cooling to −15° C. (ice/methanol bath), NaI-RN/IDS (0.378 mL, 0.378 mmol) was added dropwise. The cooling bath was removed and the resulting tan solution was stirred under nitrogen at rt for 2 h. LCMS showed complete conversion. The reaction was quenched with sodium bicarbonate solution, and diluted with ethyl acetate. The layers were separated. The organic layer was washed with brine, dried with sodium sulfate, and concentrated to give a slightly tan oil. Purification by flash column chromatography up to 10% methanol (with 2M ammonia)/methylene chloride afforded the desired product (39.5 mg, 61%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 11.17 (s, 1H), 8.53 (s, 1H), 8.49 (s, 1H), 8.12 (d, J=5.0 Hz, 1H), 7.43 (d, J=6.0 Hz, 1H), 7.33-7.26 (m, 1H), 7.05 (dt, J=7.8, 5.9 Hz, 3H), 6.34 (d, J=8.8 Hz, 1H), 6.15 (d, J=11.0 Hz, 1H), 5.36-5.25 (m, 1H), 4.63 (t, J=12.4 Hz, 2H), 4.46 (s, 1H), 3.07 (t, J=9.7 Hz, 3H), 2.62 (dd, J=23.9, 11.8 Hz, 1H), 2.49-2.26 (m, 3H), 2.21 (d, J=12.0 Hz, 1H), 2.03-1.78 (m, 3H), 1.23 (s, 9H).

Workup

  1. customto give a colorless suspension under nitrogen
  2. additionwas added dropwise
  3. customThe cooling bath was removed
  4. customThe reaction was quenched with sodium bicarbonate solution
  5. additiondiluted with ethyl acetate
  6. customThe layers were separated
  7. washThe organic layer was washed with brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customto give a slightly tan oil
  11. customPurification by flash column chromatography up to 10% methanol (with 2M ammonia)/methylene chloride

Sources & evidence

ORD record
ord-ffff6f7bf61d44aab1e605fc7b6cb097
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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