Dimethylformamide → HCID 86620039, compound

HRID 2389511Notes

Reaction equation

HRID 2389511 reaction equation
[C:1]([O:5][C:6](=[O:29])[CH2:7][N:8]1[C:12]2[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=2[N:10]=[C:9]1[S:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26](O)=[O:27])[CH:21]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[NH:59]1[C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH2:61][CH2:60]1.CN([CH:71]=[O:72])C>>[N:59]1([C:26]([C:22]2[CH:23]=[CH:24][C:25]([O:72][CH3:71])=[C:20]([CH:21]=2)[CH2:19][S:18][C:9]2[N:8]([CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:29])[C:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=3[N:10]=2)=[O:27])[C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH2:61][CH2:60]1

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 10328IndolineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131729957HCID 131729957, compound

Product 1

HCID 86620039HCID 86620039, compound

Procedure

To a solution of tert-butyl[2-(3-hydroxycarbonyl-benzylsulfanyl)-5-fluoro-benzoimidazol-1-yl]-acetate (Precursor 5-F-H-00b, 44.6 mg, 0.1 mmol) in dry DMF (0.8 ml) are added successively Et3N (21.1 μl, 15.2 mg, 0.15 mmol, 1.5 eq.), HOBt (23.0 mg, 0.15 mmol, 1.5 eq.), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (28.8 mg, 0.15 mmol, 1.5 eq.) and indoline (16.8 μl, 17.9 mg, 0.15 mmol, 1.5 eq.). The reaction mixture is stirred at rt overnight. The solvents are evaporated under reduced pressure, dichloromethane (4 ml) is added and the resulting organic phase is washed once with 2 ml of a 1 M NaHCO3 solution in water and once with 2 ml of a 1 M solution of sodium hydrogen sulfate in water. The acidic aqueous phase was extracted once with dichloromethane (2 ml). The combined organic phase is washed with brine. The solvent is removed under a stream of air and the resulting crude product is dried under high vacuum overnight yielding the title compound (40 mg) in 83% as a light brown oil: tR=1.20 min (LC-3), ESI-MS (pos.): m/z 548.23 [M+H]+, 1H-NMR (CDCl3): δ (ppm) 1.400 (s, 9H, tBu), 2.95 (t, 2H, NCH2CH2Ar), 3.91 (s, 3H, OCH3), 3.95 (t, 2H, NCH2CH2Ar), 4.65 (s, 2H, SCH2), 4.72 (s, 2H, CH2CO2), 6.91-7.19 (m, 7Harom), 7.45 (m, 1Harom), 7.52 (m, 1Harom), 7.64 (m, 1Harom).

Workup

  1. customThe solvents are evaporated under reduced pressure, dichloromethane (4 ml)
  2. additionis added
  3. washthe resulting organic phase is washed once with 2 ml of a 1 M NaHCO3 solution in water and once with 2 ml of a 1 M solution of sodium hydrogen sulfate in water
  4. extractionThe acidic aqueous phase was extracted once with dichloromethane (2 ml)
  5. washThe combined organic phase is washed with brine
  6. customThe solvent is removed under a stream of air
  7. dry with materialthe resulting crude product is dried under high vacuum overnight

Sources & evidence

ORD record
ord-4bac018a9b21426ab937ca3dd20fc1a2
Source dataset
uspto-grants-2012_09
Patent number
US08273740B2

Reaction notes

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