Water → (S)-4-(5,7-dibromo-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)-3-methoxypropyl]-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine

HRID 1060620Notes

Reaction equation

HRID 1060620 reaction equation
ClC1C2N=NN([C@H](COC)CCOC)C=2C=C(C)N=1.[Br:20][C:21]1[CH:22]=[C:23]2[C:27](=[C:28]([Br:30])[CH:29]=1)[N:26]([C:31]1[C:36]3[N:37]=[N:38][N:39]([C@H:40]([CH2:45][O:46][CH3:47])[CH2:41][CH2:42][O:43][CH3:44])[C:35]=3[CH:34]=[C:33]([CH3:48])[N:32]=1)[CH2:25][CH2:24]2.BrC1C=C2C(=C(Br)C=1)NCC2.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O>C1COCC1>[Br:20][C:21]1[CH:22]=[C:23]2[C:27](=[C:28]([Br:30])[CH:29]=1)[N:26]([C:31]1[C:36]3[N:37]=[N:38][N:39]([C@H:40]([CH2:45][O:46][CH3:47])[CH2:41][CH2:42][O:43][CH3:44])[C:35]=3[CH:34]=[C:33]([CH3:48])[N:32]=1)[CH2:25][CH2:24]2

Participants

6

Reactant 4

HCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 18629224HCID 18629224, compoundHCID 86583721(S)-4-(5,7-Dibromo-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)-3-methoxypropyl]-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine (S)-4-chloro-1-(1-methoxymethyl-3-methoxypropyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine

Product 1

HCID 9936650(S)-4-(5,7-dibromo-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)-3-methoxypropyl]-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridineYield 85.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

Part J:(S)-4-(5,7-Dibromo-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)-3-methoxypropyl]-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine (S)-4-chloro-1-(1-methoxymethyl-3-methoxypropyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine (0.72 g, 2.54 mmol) and 5,7-dibromoindoline (0.72 g, 2.60 mmol) were dissolved in anhydrous THF (6 mL) and cooled in an ice bath. To that a 1 M solution of NaHMDS in THF (3.0 mL, 3.0 mmol) was added and the reaction was stirred for 20 min, allowed to warm to 25° C. and stirred for 3 h. Then water (30 mL) was added and the mixture was extracted twice with EtOAc (80 and 40 mL). The combined organic extracts was washed with brine (30 mL) dried (MgSO4) and stripped in vacuo. The residue was chromatographed on silica gel using 40% EtOAc/hexanes as eluent to give the product (1.14 g, 85% yield).

Workup

  1. temperaturecooled in an ice bath
  2. stirringstirred for 3 h
  3. extractionthe mixture was extracted twice with EtOAc (80 and 40 mL)
  4. washThe combined organic extracts was washed with brine (30 mL)
  5. dry with materialdried (MgSO4)
  6. customThe residue was chromatographed on silica gel using 40% EtOAc/hexanes as eluent

Sources & evidence

ORD record
ord-23d5e2dcaf2541ef87b765a4ed809fbb
Source dataset
uspto-grants-2003_02
Patent number
US06525056B2

Reaction notes

Loading…