Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:10](#[N:13])[CH:11]=[CH2:12].N12CCN(CC1)CC2>[OH-].[Na+]>[O:1]1[C:2]2[C:3](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:11]([C:10]#[N:13])[CH2:12]1
Reactant: O=Cc1ccccc1O
Reactant: C=CC#N
Agent: C1CN2CCN1CC2
Agent: [Na+]
Agent: [OH-]
Product: N#CC1=Cc2ccccc2OC1
Temperature: 90 °C

Procedure:
A microwave vessel was charged with 2-hydroxybenzaldehyde (Aldrich, 3.0 mL, 28.6 mmol), acrylonitrile (9.4 mL, 143 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.80 g, 7.2 mmol), and heated in a microwave Personal Chemistry at 90° C. for 13 hours. Sodium hydroxide (1N, 200 mL) was added and the mixture was extracted twice with ethyl acetate (200 mL), and the combined organic layer washed with brine, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 0-to-20% ethyl acetate in hexane providing the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 4.88 (d, J=1.36 Hz, 2H), 6.90 (d, J=8.14 Hz, 1H), 7.01 (td, J=7.46, 1.01 Hz, 1H), 7.30 (m, 2H), 7.58 (s, 1H). MS (DCI) m/z 175.05 (M+NH4)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:23])[CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([CH2:17]OS(C)(=O)=O)[CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C-:24]#[N:25].[Na+]>CN(C)C=O.CCOCC>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([CH2:17][C:24]#[N:25])[CH2:13][CH2:12]1)[CH3:23])([CH3:4])([CH3:3])[CH3:2]
Reactant: [C-]#N
Reactant: CN(CC[C@H]1CC[C@H](COS(C)(=O)=O)CC1)C(=O)OC(C)(C)C
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CN(CC[C@H]1CC[C@H](CC#N)CC1)C(=O)OC(C)(C)C

Procedure:
A solution of 12.64 g (36.17 mmol) of trans-methanesulfonic acid 4-[2-(tert-butoxycarbonyl-methyl-amino)-ethyl]-cyclohexylmethyl ester (example 13.1) and 4.51 g (92 mmol) of sodium cyanide in 100 ml of dimethylformamide was stirred for 6 hours at 110° C. The reaction mixture was then taken up in ether and washed four times with water. The ether layer was dried over sodium sulfate and concentrated under reduced pressure, giving 10.14 g of crude trans-[2-(4-cyanomethyl-cyclohexyl)-ethyl]-methyl-carbamic acid tert-butyl ester as a colorless oil, which was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:12][CH:11]=2)[C:5]([C:20]#[N:21])=[C:4]([S:22]C2C=CC=CC=2)[N:3]=1.[S-2].[Na+].[Na+].Cl>CN(C=O)C.O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=2)[C:5]([C:20]#[N:21])=[C:4]([SH:22])[N:3]=1
Reactant: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(Sc3ccccc3)c2C#N)cc1
Agent: Cl
Agent: [Na+]
Agent: [S-2]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)Nc1ccc(-c2c(C#N)c(N)nc(S)c2C#N)cc1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
30.83 g (80 mmol) of N-{4-[2-amino-3,5-dicyano-6-(phenylsulphanyl)-4-pyridinyl]-phenyl}-acetamide are dissolved in 120 ml of DMF under argon, after which 9.36 g (120 mmol) of sodium sulphide are added and the mixture is stirred at 80° C. for 2 hours. A solution of 20 ml of 1N aqueous HCl in 44 ml of water is then added dropwise at from 40 to 65° C., after which the crystals which have formed during this procedure are filtered off with suction and washed with water. The precipitate is suspended in 200 ml of methanol and stirred under reflux for 5 minutes. After cooling down to room temperature, the precipitate is filtered off with suction, washed with methanol and diethyl ether and dried in vacuo.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH2:19])([CH3:4])([CH3:3])[CH3:2].C([O:23][C:24](=O)[CH2:25][C:26](=[O:38])[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([N:33]2[CH:37]=[CH:36][N:35]=[N:34]2)[CH:28]=1)C>>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH:19][C:24](=[O:23])[CH2:25][C:26](=[O:38])[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([N:33]2[CH:37]=[CH:36][N:35]=[N:34]2)[CH:28]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Reactant: CCOC(=O)CC(=O)c1cccc(-n2ccnn2)c1
Product: Cc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3ccnn3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared from (2-amino-5-methyl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J15) (290 mg, 1.0 mmol) and 3-oxo-3-(3-[1,2,3]triazol-1-yl-phenyl)-propionic acid ethyl ester (Example K1) (259 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow oil (300 mg, 60%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([Br:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]([NH2:19])=[S:18])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:21][C:22](=O)[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>C(O)C>[CH2:1]([O:8][C:9]1[C:14]([Br:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]2[S:18][CH:21]=[C:22]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:19]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(CBr)CCc1ccccc1
Reactant: NC(=S)Nc1cc(OCc2ccccc2)c(Br)cn1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Brc1cnc(Nc2nc(CCc3ccccc3)cs2)cc1OCc1ccccc1
Temperature: 75 °C
Reaction time: 8 h
Yield: 78.7 %

Procedure:
A flask was charged with 1-(4-(benzyloxy)-5-bromopyridin-2-yl)thiourea (2.34 g, 6.92 mmol), 1-bromo-4-phenylbutan-2-one (1.65 g, 7.26 mmol), and triethylamine (1.93 ml, 13.8 mmol). Ethanol (100 mL) was added and the reaction was stirred at 75° C. for 8 hours. The reaction was cooled and filtered, and the collected solids were washed with water to give the desired product (2.54 g, 77.9% yield) as a white solid.
Reaction SMILES: C(O[C:9]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([N:19]2[CH:23]=[CH:22][N:21]=[C:20]2[CH3:24])=[C:16]([F:18])[CH:17]=1)=O)C1C=CC=CC=1.C([Li])CCC.[CH2:30]([O:34][C:35](=[O:39])CCC)[C@@H:31]1[O:33]C1.C(=O)(O)[O-].[Na+]>O1CCCC1.CN1CCCN(C)C1=O>[F:18][C:16]1[CH:17]=[C:12]([N:11]2[CH2:9][C@H:30]([CH2:31][OH:33])[O:34][C:35]2=[O:39])[CH:13]=[CH:14][C:15]=1[N:19]1[CH:23]=[CH:22][N:21]=[C:20]1[CH3:24]
Reactant: CCCC(=O)OC[C@H]1CO1
Reactant: Cc1nccn1-c1ccc(NC(=O)OCc2ccccc2)cc1F
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Product: Cc1nccn1-c1ccc(N2C[C@H](CO)OC2=O)cc1F
Reaction time: 0.5 h
Yield: 44.5 %

Procedure:
5-Benzyloxycarbonylamino-2-(2-methylimidazol-1-yl)fluorobenzene (54 g, 0.166 M) was dissolved in a mixture of dry tetrahydrofuran (600 ml) and 1,3-dimethyl-2,4,5,6-tetrahydro-2(1H)-pyrimidinone (100 ml) under nitrogen, cooled to −70°, and treated with a solution of n-butyllithium (1.6 M in isohexane, 114 ml), over 30 minutes. After stirring for 30 minutes at −70°, a solution of (R)-glycidylbutyrate (26.35 g, 0.183 M) in dry tetrahydrofuran (50 ml) was added over 15 minutes. Stirring was continued for 16 hours allowing the temperature to rise to ambient. The mixture was treated with aqueous sodium bicarbonate.(5%, 500 ml) and ethyl acetate (800 ml), the organic layer separated, and the aqueous extracted with further ethyl acetate (3×750 ml). The combined extracts were dried (magnesium sulfate) and evaporated, and the resulting oil triturated with diethyl ether. The resulting solid was recrystallised from isopropanol to give the title compound (21.5 g). NMR (DMSO-d6) δ: 2.16 (s, 3H); 3.56 (dt, 1H); 3.69 (dt, 1H); 3.88 (dd, 1H); 4.15 (t, 1H); 4.74 (m, 1H); 5.24 (t, 1H); 6.92 (s, 1H); 7.20 (s, 1H); 7.48 (dd, 1H); 7.53 (t, 1H); 7.74 (dd, 1H). MS (ESP): 292 (MH+) for C14H14FN3O3
Reaction SMILES: [OH-].[Li+].[F:3][C:4]([F:20])([CH:17]([F:19])[F:18])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([O:15]C)=[O:14])=[N:11][CH:12]=1>C1COCC1.O>[F:20][C:4]([F:3])([CH:17]([F:19])[F:18])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([OH:15])=[O:14])=[N:11][CH:12]=1
Reactant: COC(=O)c1ccc(OCC(F)(F)C(F)F)cn1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1ccc(OCC(F)(F)C(F)F)cn1
Temperature: 60 °C
Reaction time: 1 h
Yield: 92.8 %

Procedure:
Lithium hydroxide (469 mg, 19.6 mmol) is added to a solution of methyl 5-(2,2,3,3-tetrafluoropropoxy)pyridine-2-carboxylate (1.047 mg, 3.92 mmol) in THF (7 mL) and water (7 mL). The reaction mixture is stirred for 1 hour at 60° C., cooled to ambient temperature, quenched with 1 M HCl (20 mL), diluted with brine and extracted with dichloromethane (3 times). The organic layers are combined, dried over MgSO4, filtered, and concentrated under reduced pressure to give the title compound (921 mg, 93%). ES/MS (m/e): 254.0 (M+1).
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:20][C:21]([NH:23][C@H:24]([C:40](O)=[O:41])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[NH2:58][C@H:59]([C:63]([OH:65])=[O:64])[C@@H:60]([CH3:62])[OH:61]>>[C:1]([O:18][CH:19]([CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:20][C:21]([NH:23][C@H:24]([C:40]([NH:58][C@H:59]([C:63]([OH:65])=[O:64])[C@@H:60]([CH3:62])[OH:61])=[O:41])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: C[C@@H](O)[C@H](N)C(=O)O
Reactant: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Product: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)O)[C@@H](C)O
Yield: 79.5 %

Procedure:
Starting from Nα -(3-hexadecanoyloxyoctadecanoyl)-Nε -benzyloxycarbonyl-L-lysine (2.68 g) prepared by the method of Example 20 (1), and L-threonine (0.95 g), N-[Nα -(3-hexadecanoyloxyoctadecanoyl)-Nε -benzyloxycarbonyl-L-lysyl]-L-threonine (2.4 g) was obtained as crystals according to a similar manner to that of Example 32.
Reaction SMILES: F[C:2]1[CH:20]=[CH:19][C:5]([C:6]([N:8]([CH2:14][C:15]([F:18])([F:17])[F:16])[CH2:9][C:10]([F:13])([F:12])[F:11])=[O:7])=[CH:4][C:3]=1[N+:21]([O-:23])=[O:22].[NH2:24][CH2:25][CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.CCN(CC)CC>CCO>[N+:21]([C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][C:2]=1[NH:24][CH2:25][CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[C:6]([N:8]([CH2:14][C:15]([F:18])([F:16])[F:17])[CH2:9][C:10]([F:12])([F:11])[F:13])=[O:7])([O-:23])=[O:22]
Reactant: NCC1CCOCC1
Reactant: O=C(c1ccc(F)c([N+](=O)[O-])c1)N(CC(F)(F)F)CC(F)(F)F
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=C(c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)N(CC(F)(F)F)CC(F)(F)F

Procedure:
Following the general procedure for Intermediate 2 using 4-fluoro-3-nitro-N,N-bis(2,2,2-trifluoroethyl)benzamide (75 mg, 0.215 mmol) and 4-aminomethyltetrahydropyran (27 mg, 0.236 mmol) in 3 mL of EtOH containing Et3N (0.045 mL, 0.323 mmol). The product was purified by flash chromatography on silica gel using 2:1/hexanes:EtOAc as eluent. Yield: 87 mg (91%); 1H NMR (CDCl3) 1.47 (m, 2H), 1.75 (m, 2H), 1.98 (m, 1H), 3.27 (t, J=5.47 Hz, 2H), 3.43 (m, 2H), 4.03 (m, 2H), 4.24 (q, J=8.33 Hz, 6H), 6.93 (d, J=8.98 Hz, 1H), 7.54 (d, J=8.98 Hz, 1H), 8.30 (s, 1H), 8.40 (brs, 1H); MS (ESI) 444.31 (MH+).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[C:18]2[CH:17]=[C:16]([C:19]([F:22])([F:21])[F:20])[CH:15]=[CH:14][C:13]=2[S:12][C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2.C(N(CC)CC)C.[CH2:30]([C:32]1([O:38][CH2:39][CH2:40][OH:41])[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[CH3:31]>C(C(C)=O)C.[I-].[Na+]>[ClH:1].[F:20][C:19]([F:22])([F:21])[C:16]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH2:4][CH2:3][CH2:2][N:35]3[CH2:36][CH2:37][C:32]([O:38][CH2:39][CH2:40][OH:41])([CH2:30][CH3:31])[CH2:33][CH2:34]3)[C:18]=2[CH:17]=1
Reactant: CCC1(OCCO)CCNCC1
Reactant: FC(F)(F)c1ccc2c(c1)N(CCCCl)c1ccccc1S2
Agent: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Solvent: CCN(CC)CC
Product: CCC1(OCCO)CCN(CCCN2c3ccccc3Sc3ccc(C(F)(F)F)cc32)CC1
Product: Cl
Yield: 47.6 %

Procedure:
37.7 g of 10-(3-chloropropyl)-2-trifluoromethyl-phenothiazine were dissolved in 100 ml of methyl ethyl ketone and 16.5 g of sodium iodide, 11.1 g of triethylamine and then 19 g of 2-(4-ethyl-4-piperidyloxy)-ethanol dissolved in 100 ml of methyl ethyl ketone were successively added thereto. The mixture was refluxed for 20 hours and after cooling, the precipitate formed was removed by vacuum filtration. The filtrate was evaporated to dryness and the residue was dissolved in methylene chloride. The organic solution was washed with an aqueous solution of sodium bicarbonate, then with water, dried and concentrated to dryness. The residue was dissolved in an ethanol-ether mixture to which was added an ether solution of hydrogen chloride. The precipitate formed was recovered by vacuum filtration and was crystallized from isopropanol, then from acetonitrile to obtain 27 g of 2-trifluoromethyl-10-[3-(4-β-hydroxyethoxy-4-ethyl-piperidino)-propyl]-phenothiazine hydrochloride as white crystals, melting at 204° C and soluble in chloroform, water, dilute hydrochloride acid and methylene chloride.
Reaction SMILES: CS(C)=O.[N+:5](/[CH:8]=[CH:9]/[C:10]1[CH:22]=[CH:21][C:13]([O:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:12][CH:11]=1)([O-:7])=[O:6].C(O)(=O)C.[BH4-].[Na+]>O>[N+:5]([CH2:8][CH2:9][C:10]1[CH:22]=[CH:21][C:13]([O:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:12][CH:11]=1)([O-:7])=[O:6]
Reactant: O=[N+]([O-])/C=C/c1ccc(Oc2cccnc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: O=[N+]([O-])CCc1ccc(Oc2cccnc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 40.6 %

Procedure:
To a dimethyl sulfoxide (15.0 mL) solution of 3-(4-((E)-2-nitro-vinyl)-phenoxy)-pyridine (2.00 g, 8.26 mmol) described in Manufacturing Example 76-1-2 and acetic acid (2.00 mL) was added sodium borohydride (500 mg, 13.2 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 30 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3->1:2) to obtain the title compound (819 mg, 40.6%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].C([O-])([O-])=O.[K+].[K+].[CH2:18](Cl)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC(C)=O>[CH2:18]([O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: COc1cc(C#N)ccc1O
Reactant: ClCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COc1cc(C#N)ccc1OCc1ccccc1
Temperature: 25 °C
Yield: 88.9 %

Procedure:
To 4-hydroxy-3-methoxybenzonitrile (20.0 g, 134 mmol) in acetone (200 ml) were added K2CO3 (55.6 g, 402 mmol) and benzyl chloride (23.2 ml, 201 mmol). The resulting reaction mixture was refluxed overnight. After cooling to room temperature, acetone was removed by evaporation under reduced pressure and the residue was recrystallized to obtain 4-benzyloxy-3-methoxy-benzonitrile(28.5 g, 88%). Then, according to the similar procedure of Example 1, 7-(4-Benzyloxy-3-methoxy-phenyl)-5-ethylsulfanyl-imidazo[1,2-c]pyrimidine was prepared.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@@H:6]1Br)(=[O:3])[CH3:2].[N-:25]=[N+]=[N-].[Li+].CC(C)=O>C(Cl)(Cl)Cl.O>[C:1]([NH:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[NH2:25])(=[O:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)N[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O[C@@H]1Br
Agent: [Li+]
Solvent: CC(C)=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(=O)N[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O[C@H]1N

Procedure:
2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosylamine was prepared as follows. 2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl bromide (11.25 g, 30.8 mmol) was reacted with lithium azide (2.25 g, 46 mmol) in refluxing acetone (50 ml) under nitrogen atmosphere for 19 hr. The acetone was then removed under reduced pressure to give a semi-solid residue, which was taken up in a mixture of chloroform and water. The organic layer was separated, dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated to dryness to give the crude azo-saccharide as a brownish residue. This residue was dissolved in ethyl acetate and decolorized with activated carbon. Addition of ether to the ethyl acetate containing the product yielded the sugar azide as a white precipitate. TLC on silica (methanol:chloroform/1:9) showed a single homogenous spot. The resulting azide (4.0 g) was hydrogenated over platinum oxide (0.3 g) at room temperature and atmospheric pressure. After the completion of the reaction, the catalyst was filtered off and the solution was evaporated to dryness to give the aminosaccharide (3.4 g) as a white solid. TLC gave one spot (methanol:chloroform/1:9).
Reaction SMILES: C[O:2][C:3](=[O:31])[CH2:4][CH:5]1[C:9]2=[C:10]([S:23][C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[C:11]3[C:12]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:13][C:14]([O:17][CH3:18])=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6]1.[Li+].[OH-]>C1COCC1.CO.CC(O)=O>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([S:23][C:10]2[C:11]3[C:12]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:13][C:14]([O:17][CH3:18])=[CH:15][C:16]=3[N:8]3[CH2:7][CH2:6][CH:5]([CH2:4][C:3]([OH:31])=[O:2])[C:9]=23)=[CH:25][CH:26]=1
Reactant: COC(=O)CC1CCn2c1c(Sc1ccc(Cl)cc1)c1c(S(C)(=O)=O)cc(OC)cc12
Agent: [Li+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc(S(C)(=O)=O)c2c(Sc3ccc(Cl)cc3)c3n(c2c1)CCC3CC(=O)O
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 89.4 %

Procedure:
To a solution of the ester from Step 7 (23 mg, 0.048 mmol) in THF (3 mL) and MeOH (1 mL) at RT was added 1M LiOH (0.24 mL, 0.24 mmol). After stirring at r.t. for 4.5 hours, HOAc (10 drops) was added and the solvent was evaporated. The residue was taken up in EtOAc/H2O and the organic phase was washed with brine, dried (MgSO4), and filtered. Upon removal of the solvent, the resulting solid was stirred with 1:5 EtOAc:hexane to give a beige solid (20 mg).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH2:7]([O:14][CH2:15][CH2:16][CH:17]=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C[Si]([C:23]#[N:24])(C)C.C(N(S(F)(F)[F:31])CC)C>[I-].[Zn+2].[I-]>[CH2:7]([O:14][CH2:15][CH2:16][CH:17]([F:31])[C:23]#[N:24])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=CCCOCc1ccccc1
Reactant: C[Si](C)(C)C#N
Reactant: CCN(CC)S(F)(F)F
Agent: O=C(Cl)C(=O)Cl
Agent: [I-]
Agent: [Zn+2]
Product: N#CC(F)CCOCc1ccccc1

Procedure:
The compound 1,3-propanediol 13 is mono-alkylated to yield the 3-benzyloxy-1-propanol, which is then oxidized by means of oxalyl chloride to the corresponding 3-benzyloxy-1-propanal, 15. Reaction with trimethylsilylcyanide, preferably in the presence of a catalytic amount of zinc iodide, followed by treatment with diethylaminosulfurtrifluoride results in the formation of 4-benzyloxy-2-fluorobutyronitrile, 16.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:23]2[CH:27]=[N:26][N:25]=[N:24]2)=[C:6]([CH:22]=1)[CH2:7][NH:8][C:9]([C@@H:11]1[CH2:14][CH2:13][N:12]1C(OC(C)(C)C)=O)=[O:10].CCOC(C)=O.[ClH:34]>>[Cl-:1].[Cl-:34].[NH2+:12]1[CH2:13][CH2:14][C@H:11]1[C:9]([NH:8][CH2:7][C:6]1[CH:22]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[N:23]1[CH:27]=[NH+:26][N:25]=[N:24]1)=[O:10]
Reactant: CC(C)(C)OC(=O)N1CC[C@H]1C(=O)NCc1cc(Cl)ccc1-n1cnnn1
Reactant: Cl
Solvent: CCOC(C)=O
Product: O=C(NCc1cc(Cl)ccc1-n1c[nH+]nn1)[C@@H]1CC[NH2+]1
Product: [Cl-]

Procedure:
Through a solution of tert-butyl (2S)-2-({[5-chloro-2-(1H-tetraazol-1-yl)benzyl]amino}carbonyl)azetidine-1-carboxylate (467 mg, 1.19 mmol) in EtOAc (24.0 mmol) at 0° C. was bubbled HCl (g) for 10 min. The solvent was removed in vacuo to give the title compound as a yellow solid. LCMS (M+H): 293.0. 1H NMR (CD3OD, 400 MHz): δ 9.57 (s, 1 H), 7.72–7.70 (m, 1 H), 7.64–7.59 (m, 1 H), 7.54–7.52 (m, 1 H), 4.96–4.92 (m, 1 H), 4.34–4.21 (m, 2 H), 4.13–4.06 (m, 1 H), 3.97–3.90 (m, 1 H), 2.81–2.75 (m, 1 H), 2.51–2.45 (m, 1 H).
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:23][C@H:22]([CH2:24][OH:25])[O:21][C:20]4=[O:26])=[CH:15][C:14]=3[F:27])=[CH:9][N:8]=2)=[N:3]1.[CH3:28][S:29](Cl)(=[O:31])=[O:30].C(N(CC)CC)C.O>C(Cl)Cl.[Cl-].[Na+].O>[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:23][C@H:22]([CH2:24][O:25][S:29]([CH3:28])(=[O:31])=[O:30])[O:21][C:20]4=[O:26])=[CH:15][C:14]=3[F:27])=[CH:9][N:8]=2)=[N:3]1
Reactant: Cn1nnc(-c2ccc(-c3ccc(N4C[C@H](CO)OC4=O)cc3F)cn2)n1
Reactant: CS(=O)(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: Cn1nnc(-c2ccc(-c3ccc(N4C[C@H](COS(C)(=O)=O)OC4=O)cc3F)cn2)n1
Reaction time: 0.5 h
Yield: 82.6 %

Procedure:
In 14 ml of methylene chloride was dissolved 1 g of (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one (compound 10). The solution was added with 0.46 g of methanesulfonylchloride 0.46 g and 0.75 ml of triethylamine at room temperature and stirred at the same temperature for 30 minutes. Water and brine were added to the reaction mixture for washing, followed by extraction. The organic layer was dehydrated, filtrated and concentrated in vacuo thereby to provide (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-methanesulfonyloxymethyl oxazolidin-2-one 1 g. Yield 82%.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)C=C.Cl[C:20]1[CH:25]=CC=C[C:21]=1Cl>>[F:18][C:15]1[CH:14]=[CH:13][C:12]([O:11][C:8]2[CH:7]=[CH:6][C:5]([OH:4])=[C:10]([CH2:25][CH:20]=[CH2:21])[CH:9]=2)=[CH:17][CH:16]=1
Reactant: Clc1ccccc1Cl
Reactant: C=CCOc1ccc(Oc2ccc(F)cc2)cc1
Product: C=CCc1cc(Oc2ccc(F)cc2)ccc1O

Procedure:
4-(4-fluorophenoxy)phenyl allyl ether (4.00 g, 16.37 mmol) was taken up in 1,2-dichlorobenzene (50 mL) and refluxed for 48 h. After cooling, the solvent was removed in vacuo and the resulting crude oil was chromatographed on silica gel (15% ethyl acetate/hexane) to afford the title compound.