Methyl iodide → HCID 68309840, compound

HRID 529572Notes

Reaction equation

HRID 529572 reaction equation
[CH2:1]([C@@H:8]([CH2:26][CH2:27][C@H:28]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:29]([NH:31][C@H:32]1[CH2:38][CH2:37][S:36][C@H:35]2[CH2:39][CH2:40][CH2:41][C@@H:42]([CH2:43][OH:44])[N:34]2[C:33]1=[O:45])=[O:30])[C:9]([NH:11][C@H:12]1[CH2:18][CH2:17][S:16][C@H:15]2[CH2:19][CH2:20]C[C@@H](CO)[N:14]2[C:13]1=[O:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:53]C([O-])(C)C.[K+].IC.[CH2:61]1[CH2:65][O:64][CH2:63][CH2:62]1>>[CH2:46]([C@@H:28]([CH2:27][CH2:26][C@H:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9]([NH:11][C@H:12]1[CH2:18][CH2:17][S:16][C@H:15]2[CH2:19][CH2:20][CH2:62][C@@H:61]([CH2:65][O:64][CH3:63])[N:14]2[C:13]1=[O:25])=[O:10])[C:29]([NH:31][C@H:32]1[CH2:38][CH2:37][S:36][C@H:35]2[CH2:39][CH2:40][CH2:41][C@@H:42]([CH2:43][O:44][CH3:53])[N:34]2[C:33]1=[O:45])=[O:30])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

5

Reactant 4

HCID 6328Methyl iodide2×HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxide2×HCID 68311184HCID 68311184, compound

Product 1

HCID 68309840HCID 68309840, compoundYield 12%

Procedure

To a round bottom flask at 0° C. was added (2R,5R)-2,5-dibenzyl-N1,N6-bis((4S,7S,10aS)-7-(hydroxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-yl)hexanediamide (24.4 mg, 0.032 mmol), THF (0.15 mL) and followed by KOtBu (1.0M in THF, 0.0715 mL, 0.071 mmol). The reaction was then warmed to rt and stirred for 15 min. Then, iodomethane (18.5 mg, 0.130 mmol) was added. The reaction was stirred at rt for 4 hr. LC/MS showed a mixture of starting material, mono-ether product and desired di-ether product. Another 71 μL of KOtBu solution was added along with another 8 μL of iodomethane. The reaction mixture was stirred at rt overnight. The reaction mixture was quenched by addition of saturated aqueous NH4Cl. The solution was partitioned between EtOAc and water. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified by RP prep-HPLC (Method A). The fraction containing the product was concentrated to give (2R,5R)-2,5-dibenzyl-N1,N6-bis((4S,7S,10aS)-7-(methoxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-yl)hexanediamide (3.0 mg, 0.0037 mmol, 12% yield) of a white solid. Anal. Calcd. for C42H58N4O6S2 m/z 778.5. found: 779.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.25-7.20 (4H, m), 7.18-7.11 (6H, m), 6.97-6.91 (2H, m), 5.28-5.23 (2H, m), 4.96-4.89 (2H, m), 4.71-4.65 (2H, m), 3.73-3.67 (2H, m), 3.41-3.36 (2H, m), 3.35 (6H, s), 3.23-3.15 (2H, m), 2.85-2.78 (2H, m), 2.73-2.64 (4H, m), 2.40-2.31 (2H, m), 2.09-1.95 (4H, m), 1.92-1.77 (4H, m), 1.72-1.62 (4H, m), 1.61-1.53 (4H, m), 1.51-1.44 (2H, m), 1.40-1.31 (2H, m).

Workup

  1. stirringThe reaction was stirred at rt for 4 hr
  2. stirringThe reaction mixture was stirred at rt overnight
  3. customThe reaction mixture was quenched by addition of saturated aqueous NH4Cl
  4. customThe solution was partitioned between EtOAc and water
  5. customThe organic phase was isolated
  6. washwashed with saturated aqueous NaCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by RP prep-HPLC (Method A)
  11. additionThe fraction containing the product
  12. concentrationwas concentrated

Sources & evidence

ORD record
ord-99d5cf32ef43456bb08187fb27657e8c
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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