Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50]4(O[C@H](C5C=CC=CC=5)[C@@H](C5C=CC=CC=5)[O:51]4)[CH2:49]3)/[C:44](O)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:30][CH2:29]1.[NH2:69][C:70]1[S:71][C:72]2[C:77]([N:78]=1)=[CH:76][CH:75]=[C:74]([O:79][CH2:80][C:81]([O:83]CC)=O)[N:73]=2.C(=O)(O)[O-].[Na+]>ClCCl.N1C=CC=CC=1>[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50](=[O:51])[CH2:49]3)/[C:44]([NH:69][C:70]3[S:71][C:72]4[C:77]([N:78]=3)=[CH:76][CH:75]=[C:74]([O:79][CH2:80][CH2:81][OH:83])[N:73]=4)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:29][CH2:30]1
Reactant: O=C(O)/C(=C/[C@H]1CCC2(C1)O[C@H](c1ccccc1)[C@@H](c1ccccc1)O2)c1ccc(S(=O)(=O)C2CC2)c(C2CC2)c1
Reactant: CCOC(=O)COc1ccc2nc(N)sc2n1
Agent: O=C([O-])O
Agent: O=C1CCC(=O)N1Br
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C1CC[C@H](/C=C(/C(=O)Nc2nc3ccc(OCCO)nc3s2)c2ccc(S(=O)(=O)C3CC3)c(C3CC3)c2)C1
Temperature: 5 °C
Reaction time: 0.25 h
Yield: 14.9 %

Procedure:
To a solution of triphenylphosphine (600 mg) in dichloromethane (10 mL) was added N-bromosuccinimide (400 mg) under ice-cooling (at an internal temperature of 5° C. or lower), followed by stirring for 15 minutes, and then a solution of (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]acrylic acid (600 mg) in dichloromethane (10 mL) was added thereto under ice-cooling, followed by stirring at room temperature for 20 minutes. To the reaction mixture were added a mixture of ethyl 2-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]acetate (270 mg) in dichloromethane (10 mL) and pyridine (0.17 mL), followed by stirring at room temperature overnight. A saturated sodium bicarbonate solution and dichloromethane were added thereto, and the organic layer was sequentially washed with 1 M hydrochloric acid and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate). To the obtained colorless amorphous in THF (3 mL)-methanol (3 mL) mixed solution was added 1 M aqueous sodium hydroxide solution (0.6 mL), followed by stirring at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, followed by addition of 1 M hydrochloric acid and ethyl acetate, and the organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained colorless amorphous in dioxane (5 mL) was added 4 M hydrochloric acid (2 mL), followed by stirring at 50° C. for 3 hours and leaving it to be cooled at room temperature. The solvent was evaporated under reduced pressure, followed by addition of water and ethyl acetate and the organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxyethoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]-3-[(1S)-3-oxocyclopentyl]acrylamide (89 mg) as a colorless amorphous substance.