1-Hydroxybenzotriazole → 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(2-oxo-propane-1-sulfonyl)-phenyl]-propionamide

HRID 505589Notes

Reaction equation

HRID 505589 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH2:20][C:21](=[O:23])[CH3:22])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:47][O:48][C:49]1[N:54]=[C:53]2[S:55][C:56]([NH2:58])=[N:57][C:52]2=[CH:51][CH:50]=1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:12]=[CH:13][C:14]([S:17]([CH2:20][C:21](=[O:23])[CH3:22])(=[O:18])=[O:19])=[CH:15][CH:16]=2)[C:8]([NH:58][C:56]2[S:55][C:53]3[C:52]([N:57]=2)=[CH:51][CH:50]=[C:49]([O:48][CH3:47])[N:54]=3)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 28015575-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amineHCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochlorideHCID 674855183-Cyclopentyl-2-[4-(2-oxo-propylsulfonyl)-phenyl]-propionic acid

Product 1

HCID 115334353-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(2-oxo-propane-1-sulfonyl)-phenyl]-propionamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of the title D compound, 3-cyclopentyl-2-[4-(2-oxo-propylsulfonyl)-phenyl]-propionic acid (400 mg, 0.0011 mol) in 50 mL of DCM, HOBt (250 mg, 0.0018 mol), EDCl hydrochloride (340 mg, 0.0017 mol) and 5-methoxy-thiazolo[5,4-b]pyridin-2ylamine (235 mg, 0.0012 mol) are added followed by the addition of 0.66 mL (0.0037 mol) of DIEA. The reaction is stirred at 25° C. for 24 h, then worked up by treating it with saturated aqueous sodium bicarbonate solution. The resulting organic layer is washed with 1 N aqueous hydrochloric acid solution, followed by water and brine washings. The organic layer is dried over sodium sulfate, filtered and then evaporated under vacuum to give a brown solid. The reaction product is purified by column chromatography over Silica gel (60-120 mesh) using 80% hexane in ethyl acetate as an eluent to give 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(2-oxo-propane-1-sulfonyl)-phenyl]-propionamide as a brown solid: MS e/z (ES) 502 (M+1+, 100%); m.p. 67-71° C.; 1H NMR δ 12.71 (s, 1H), 8.02 (d, J=8.8, 1H), 7.65-7.90 (m, 4H), 6.91 (d, J=8.8, 1H), 4.69 (s, 2H), 4.08-4.12 (m, 1H), 3.90 (s, 3H), 2.19 (s, 3H), 1.78-1.82 (m, 1H), 1.60-1.75 (m, 2H), 1.43-1.55 (m, 3H), 1.30-1.42 (m, 3H), 1.00-1.20 (m 2H).

Workup

  1. washThe resulting organic layer is washed with 1 N aqueous hydrochloric acid solution
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated under vacuum
  5. customto give a brown solid
  6. customThe reaction product is purified by column chromatography over Silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-1864182f80bd420d85f81ff5ae79bb47
Source dataset
uspto-grants-2010_08
Patent number
US07781451B2

Reaction notes

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