Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[Br:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].[Cl-].[C:23]([CH2:26][C@@H:27]([O:33][C:34](=[O:47])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH2:28][N+:29]([CH3:32])([CH3:31])[CH3:30])([OH:25])=[O:24]>CN(C)C=O>[Br-:8].[C:34]([O:33][C@H:27]([CH2:26][C:23]([O:25][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH3:9])=[O:24])[CH2:28][N+:29]([CH3:30])([CH3:31])[CH3:32])(=[O:47])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46]
Reactant: CCCCCCCCCCCCCBr
Reactant: CCCCCCCCCCCCC(=O)O[C@H](CC(=O)O)C[N+](C)(C)C
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCOC(=O)C[C@H](C[N+](C)(C)C)OC(=O)CCCCCCCCCCCC
Product: [Br-]
Reaction time: 23 h
Yield: 105.7 %

Procedure:
Triethylamine (0.53 ml, 3.81 mmol) and 1-bromotridecane (5.0 g, 19.0 mmol) were added successively to a suspension of (R)-(3-carboxy-2-tridecanoyloxypropyl)trimethylammonium chloride (1.5 g, 3.81 mmol) in 30 ml of dimethylformamide, and the mixture was stirred for 23 hours at 50° to 60° C. under argon atmosphere. The solvent of the reaction mixture was removed under reduced pressure. To the residue was added 20 ml of diethyl ether, and the mixture was stirred at room temperature. Thereafter, the precipitates were collected by filtration, washed with diethyl ether, and dried to give 2.5 g of crude (R)-(2-tridecanoyloxy-3-tridecyloxycarbonylpropyl)trimethylammonium bromide as a colorless solid. To 2.5 g of the product thus obtained was added 50 ml of water, and the mixture was stirred for 1 hour at room temperature and then extracted with tetrahydrofuran-ethyl acetate (1:1). To the extracted organic layer were added 100 ml of a saturated saline solution and 30 ml of water, and the mixture was stirred for 18 hours at room temperature. Thereafter, the organic layer was collected, washed with a saturated saline solution and then water, and the solvent was removed under reduced pressure. The residue was azeotroped with ethyl acetate and then dried at room temperature under reduced pressure to afford 1.75 g of a crude desired product. The product obtained was recrystallized from ethyl acetate to provide 1.58 g of (R)-(2-tridecanoyloxy-3-tridecyloxycarbonylpropyl)trimethylammonium chloride as colorless crystals.
Reaction SMILES: C(=O)([O-])O.[Na+].[C:6](Cl)(=[O:8])[CH3:7].C1COCC1.O.[O:16]=[C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:26])[N:18]1[CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH:28]1[NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37]>C(OCC)(=O)C>[C:6]([N:30]1[CH2:31][CH2:32][CH:27]([N:18]2[C:17](=[O:16])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:26])[CH:28]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:29]1)(=[O:8])[CH3:7]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)OC(=O)NC1CNCCC1N1C(=O)c2ccccc2C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)N1CCC(N2C(=O)c3ccccc3C2=O)C(NC(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Sodium hydrogen carbonate (341 mg) and acetyl chloride (0.086 ml) were added to a THF/water (2 ml/2 ml) solution containing tert-butyl (4-(1,3-dioxoisoindolin-2-yl)piperidin-3-yl)carbamate (280 mg) obtained in the 2nd step under ice cooling, followed by stirring at room temperature for 0.5 hours. Ethyl acetate was added to the reaction solution. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. Next, the solvent was distilled away under reduced pressure. A white solid of tert-butyl (1-acetyl-4-(1,3-dioxoisoindolin-2-yl)piperidin-3-yl)carbamate (301 mg) was thus obtained.
Reaction SMILES: C[O:2][C:3]([C:5]1([CH3:15])[CH2:9][C:8]2[CH:10]=[C:11]([OH:14])[CH:12]=[CH:13][C:7]=2[O:6]1)=[O:4].C1(O)C=CC=CC=1.I[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][C:29]=1[Cl:39]>>[Cl:39][C:29]1[CH:30]=[C:31]([O:34][C:35]([F:36])([F:38])[F:37])[CH:32]=[CH:33][C:28]=1[O:27][CH2:26][CH2:25][CH2:24][O:14][C:11]1[CH:12]=[CH:13][C:7]2[O:6][C:5]([CH3:15])([C:3]([OH:2])=[O:4])[CH2:9][C:8]=2[CH:10]=1
Reactant: COC(=O)C1(C)Cc2cc(O)ccc2O1
Reactant: FC(F)(F)Oc1ccc(OCCCI)c(Cl)c1
Solvent: Oc1ccccc1
Product: CC1(C(=O)O)Cc2cc(OCCCOc3ccc(OC(F)(F)F)cc3Cl)ccc2O1

Procedure:
The title compound was prepared following the general procedure described in Example 1, Step 4, using the the intermediate prepared in Example 1, Step 1 as the phenol and the iodide prepared in Step 2.
Reaction SMILES: C=O.[O-:3][CH2:4]C.[Na+].[CH2:7]([O:9][C:10](=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[N:13]=1)[CH3:8].[C:20](OCC)(=[O:22])C>C1COCC1.CCCCCC>[CH2:7]([O:9][C:10](=[O:19])[C:11]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Br:18])[N:13]=1)([CH2:4][OH:3])[CH2:20][OH:22])[CH3:8]
Reactant: CC[O-]
Reactant: CCOC(=O)Cc1cccc(Br)n1
Reactant: CCOC(C)=O
Agent: C=O
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCOC(=O)C(CO)(CO)c1cccc(Br)n1
Reaction time: 4 h

Procedure:
To the solution of para formaldehyde (9.6 g, 319.55 mmol) and sodium ethoxide (0.87 g, 12.784 mmol) in dry THF (250 ml) was added (6-bromo-pyridin-2-yl)-acetic acid ethyl ester (31.2 g, 127.82 mmol) at 0° C. to −10° C. and allowed the reaction mixture to stir at same temperature for 4 h. Solids formed in the reaction mixture were filtered and washed with ethyl acetate and the filtrate was concentrated to obtain crude product as a brown liquid. Yield=30.0 g (crude). TLC (30% ethyl acetate in hexane) Rf=0.28; LCMS: RtH8=0.702, M+1=304.0 and 306.0.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[C:16]2[C:19](O)=[O:20])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:19]([C:16]2[C:17]3[C:12](=[CH:11][CH:10]=[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:18]=3)[CH:13]=[CH:14][CH:15]=2)=[O:20])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C(O)c1cccc2ccc(OCc3ccccc3)cc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2cccc3ccc(OCc4ccccc4)cc23)CC1

Procedure:
To the product from Step C (3.58 mmol), N-tert-butoxycarbonylpiperazine (733 mg, 3.93 mmol), EDC hydrochloride (750 mg, 3.93 mmol), HOBT (483 mg, 3.58 mmol), and triethylamine (0.498 mL, 3.58 mmol) were stirred in dry DMF (15 mL) at room temperature for two days. After concentration in vacuo, the residue was partitioned between EtOAc and 50% NaHCO3 solution, washed with water and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (30% EtOAc/hexane) to yield the desired product as a white foam.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[K+].[Br-].[CH2:19](O)[CH3:20]>>[CH2:19]([O:6][C:5](=[O:7])[C:4]1[CH:3]=[C:2]([OH:1])[CH:10]=[C:9]([OH:11])[CH:8]=1)[CH3:20]
Reactant: O=C(O)c1cc(O)cc(O)c1
Reactant: CCO
Agent: O=S(=O)(O)O
Agent: [Br-]
Agent: [K+]
Product: CCOC(=O)c1cc(O)cc(O)c1

Procedure:
To a solution of 3,5-dihydroxy benzoic acid, 1 (19 g, 123 mmol) in dry ethanol (250 mL) was added 2-3 mL of concentrated sulphuric acid drop wise and refluxed for 8 h. Ethanol was evaporated on rotavapor, diluted with water and extracted with ether. Combined ethereal layers were again washed with saturated sodium bicarbonate solution, water and dried over sodium sulphate, filtered and evaporated to dryness to afford 3. Yield 16.8 g (75%); mp 128-130° C.; MS (FAB) 183 (M++1); IR (KBr) 3496, 1819, 1687; 1H NMR (200 MHz, DMSO-d6) δ 9.89 (s, 2H), 7.06 (d, J=2.2 Hz, 2H), 6.69 (t, J=2.2 Hz, 1H), 4.48 (q, J=7.1 Hz, 2H), 1.52 (t, J=7.1 Hz, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH:4]([NH:16][C:17](=[O:23])[CH:18]([NH2:22])[CH2:19][O:20][CH3:21])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.[N+:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[S:34](Cl)(=[O:36])=[O:35])([O-:27])=[O:26].C(N(CC)CC)C.OS([O-])(=O)=O.[K+]>C1COCC1.O>[CH3:1][O:2][C:3](=[O:24])[CH:4]([NH:16][C:17](=[O:23])[CH:18]([NH:22][S:34]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[N+:25]([O-:27])=[O:26])(=[O:35])=[O:36])[CH2:19][O:20][CH3:21])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: COCC(N)C(=O)NC(Cc1ccc2ccccc2c1)C(=O)OC
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: COCC(NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)NC(Cc1ccc2ccccc2c1)C(=O)OC
Temperature: 0 °C
Reaction time: 8 h

Procedure:
2-(2-Amino-3-methoxy-propionylamino)-3-naphthalen-2-yl-propionic acid methyl ester, 58, (4.43 g, 12.1 mmol) and 2-nitrobenzene sulfonyl chloride (2.8 g, 12.7 mmol) are dissolved in any THF (20 mL). The mixture is cooled to 0° C. and triethyl amine (5 mL) is added to the reaction mixture which is then allowed to stir overnight at room temperature. Water (100 mL) is added and the reaction mixture pH adjusted to 3 with 1M KHSO4. The solution is extracted with EtOAc (3×100 mL) and the organic layers are combined and dried over Na2SO4. The solvent is removed in vacuo to afford 6.4 g (quantitative yield) of the desired product. 1H NMR (300 MHz, CDCl3, δ): 8.02 (m, 1H), 7.8 (m, 4H), 7.60 (m, 3H), 7.48 (m, 2H), 7.33 (d, J=8.3 Hz, 1H), 7.20 (d, J=8.3 Hz, 1H), 6.58 (d, J=6.25 Hz, 1H), 4.57 (quartet, J=6.25 Hz, 1H), 4.02 (quartet, J=6.25 Hz, 1H), 3.70 (s, 3H), 3.47 (m, 2H), 3.44 (m, 2H), 3.49 (s, 3H); 13C NMR, δ 171.5, 168.7, 147.9, 134.2, 133.6, 133.5, 133.2, 132.7, 131.0, 128.4, 128.3, 127.9, 127.5, 126.5, 126.1, 125.9, 72.3, 59.1, 56.6, 53.8, 52.7, 38.0.
Reaction SMILES: [OH-].[Na+].[O:3]=[CH:4][C@@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6].C(=O)C1OC=CC=1>>[CH2:4]([OH:3])[C@@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Agent: [Na+]
Agent: [OH-]
Solvent: O=Cc1ccco1
Product: OC[C@@H](O)[C@H](O)[C@@H](O)CO
Reaction time: 0.25 h

Procedure:
The fermentation medium is a sugarcane bagasse hydrolysate pretreated by dilute acid. For pretreatment, the concentration of the dilute acid is 1-4%, the operation temperature is 130° C., and the reaction time is 15 min at this temperature. In this case, NaOH is added to adjust the pH value of the hydrolysate to 6.0, the fermentation temperature is controlled at 30° C., the agitation of the incubator is maintained at 100 rpm, and the ratio of the inocula size of the culture and the volume of the fermentation medium is 1:6 (v/v). The content of xylose in the sugarcane bagasse hydrolysate is 19.8-25.8 g/L, the content of the inhibitor furfural is 0.14-0.52 g/L, the amount of xylitol produced is 7.74-12.51 g/L, and the overall utilization of xylose is 97.6-99%, as shown in Table 2.
Reaction SMILES: [CH3:1][C:2]([C:5]1[N:10]=[CH:9][C:8]([CH:11]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:12]([OH:14])=[O:13])=[CH:7][N:6]=1)([CH3:4])[CH3:3].[F:19][C:20]1[C:27]([F:28])=[C:26]([CH2:29][O:30][CH3:31])[C:25]([F:32])=[C:24]([F:33])[C:21]=1[CH2:22]O.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:4][C:2]([C:5]1[N:6]=[CH:7][C:8]([CH:11]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:12]([O:14][CH2:22][C:21]2[C:24]([F:33])=[C:25]([F:32])[C:26]([CH2:29][O:30][CH3:31])=[C:27]([F:28])[C:20]=2[F:19])=[O:13])=[CH:9][N:10]=1)([CH3:1])[CH3:3]
Reactant: CC(C)(C)c1ncc(C(C(=O)O)C(C)(C)C)cn1
Reactant: COCc1c(F)c(F)c(CO)c(F)c1F
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: COCc1c(F)c(F)c(COC(=O)C(c2cnc(C(C)(C)C)nc2)C(C)(C)C)c(F)c1F
Reaction time: 18 h

Procedure:
A solution of (RS)-2-[2-(1,1-dimethylethyl)pyrimidin-5-yl]-3,3-dimethylbutanoic acid (0.1 q), 2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl alcohol (0.089 g) and 4-dimethylaminopyridine (0.002 g) in dry dichloromethane (4 cm3) was stirred at the ambient temperature (20° C.) whilst N,N'-dicyclohexylcarbodiimide (0.084 g) was added in portions; the mixture was stirred for 18 hours. The solution was passed through silica gel and the silica gel eluted with, firstly, dichloromethane and, secondly a 50:1 mixture (by volume) of dichloromethane and ethyl acetate Evaporation of the solvents of the combined filtrate and eluted fractions gave the title compound (0.09 g) as a colourless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([NH2:9])=[C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:3]=1.[BrH:17].[N:18]#[C:19][Br:20]>C(O)C.C(Cl)Cl.C(OCC)C>[BrH:20].[BrH:17].[Cl:1][C:2]1[CH:3]=[C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:5]2[NH:9][C:19]([NH2:18])=[N:8][C:6]=2[CH:7]=1
Reactant: N#CBr
Reactant: Nc1cc(Cl)cc(CN2CCOCC2)c1N
Agent: Br
Solvent: CCO
Solvent: CCOCC
Solvent: ClCCl
Product: Nc1nc2cc(Cl)cc(CN3CCOCC3)c2[nH]1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 5-chloro-3-(morpholin-4-ylmethyl)benzene-1,2-diamine (458 mg, 1.9 mmol) in ethanol (5 mL) is added a 48% aqueous HBr solution (0.21 mL, 1.9 mmol) followed by a 3M solution of cyanogen bromide (0.95 mL, 2.8 mmol) in CH2Cl2. The reaction is stirred at room temperature for 4 h and is diluted with diethyl ether. The resulting solid is isolated by filtration to afford the title compound as the dihydrobromide salt (595 mg, 73%).
Reaction SMILES: Br[CH:2]([F:7])[C:3]([O:5][CH3:6])=[O:4].[P:8]([O:17]C(C)C)([O:13][CH:14]([CH3:16])[CH3:15])[O:9][CH:10]([CH3:12])[CH3:11]>>[CH:10]([O:9][P:8]([CH:2]([F:7])[C:3]([O:5][CH3:6])=[O:4])([O:13][CH:14]([CH3:16])[CH3:15])=[O:17])([CH3:12])[CH3:11]
Reactant: COC(=O)C(F)Br
Reactant: CC(C)OP(OC(C)C)OC(C)C
Product: COC(=O)C(F)P(=O)(OC(C)C)OC(C)C
Temperature: 150 °C
Reaction time: 5.5 h

Procedure:
Methyl bromofluoroacetate (17.1q) was mixed with triisopropyl phosphite (41.6 g) and heated with stirring at 150° C. Samples were withdrawn at intervals and analysed by GLC. After 5.5 hours, all of the initial ester had been consumed. The mixture was cooled to the ambient temperature, and excess triisopropyl phosphite was removed by distillation at reduced pressure (52° C./1.5 mm Hg). The straw-coloured residue (19.7 g was identified as substantially pure methyl diisopropylphosphonofluoroacetate.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH:4]([OH:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.N([C:16]1[NH:17][CH2:18][CH2:19][CH2:20][N:21]=1)[N+]([O-])=O>C1(C)C(C)=CC=CC=1>[NH:21]1[CH2:20][CH2:19][CH2:18][N:17]=[C:16]1[NH:1][CH2:2][CH2:3][CH:4]([OH:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: NCCC(O)c1ccccc1
Reactant: O=[N+]([O-])NC1=NCCCN1
Solvent: Cc1ccccc1C
Product: OC(CCNC1=NCCCN1)c1ccccc1

Procedure:
A mixture of 8 parts of α(2-aminoethyl)benzylalcohol, 7.2 parts of 2-(nitramino)- 1,4,5,6-tetrahydropyrimidine and 40 parts of xylene is stirred and refluxed for 48 hours with waterseparator. Upon cooling the reaction mixture, the product is separated as an oil. The xylene is decanted and the oily product is triturated in diisopropylether. The solid product is filtered off and crystallized from acetone, yielding α-[2-(1,4,5,6-tetrahydro-2-pyrimidinylamino)ethyl]benzylalcohol; m.p. 130°-135°C.
Reaction SMILES: Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([F:11])=[CH:7][CH:8]=2)/[C:3]/1=[CH:12]/[C:13]([NH2:15])=[O:14].[C:16]([O-:19])(=[O:18])[CH3:17].[K+].C1OCCOCCOCCOCCOCCOC1.C(O)(=O)C>C(#N)C.C(O)C>[C:16]([O:19][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([F:11])=[CH:7][CH:8]=2)/[C:3]/1=[CH:12]/[C:13]([NH2:15])=[O:14])(=[O:18])[CH3:17]
Reactant: CC(=O)[O-]
Reactant: NC(=O)/C=C1/c2cc(F)ccc2CC1Br
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CC#N
Solvent: CCO
Solvent: CC(=O)O
Product: CC(=O)OC1Cc2ccc(F)cc2/C1=C/C(N)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 46.5 %

Procedure:
A mixture of (Z)-2-(2-bromo-6-fluoro-1-indanylidene)acetamide (0.51 g, 1.90 mmoles), potassium acetate (0.37 g, 3.80 mmoles), and 18-crown-6 (0.06 g, 0.24 mmoles, Aldrich) in acetonitrile (20 mL) and ethanol (10 mL) was sonicated using a Sonicor ultrasonicator for 2 hours, allowing the temperature to rise to 35° C. The mixture was stirred overnight at ambient temperature. Glacial acetic acid (3 mL) was added and the mixture was sonicated for 1.5 hours allowing the temperature to rise to 50° C. The mixture was stirred overnight at ambient temperature and evaporated in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with water (2×50 mL) and evaporated in vacuo. The residue was chromatographed on silica gel eluting with hexane:ethyl acetate (3:1) gradually increasing the polarity to 100% ethyl acetate. The fractions containing the compound with Rf=0.3 in hexane:ethyl acetate (1:1) were combined and evaporated in vacuo to give a solid which was washed with hexane and dried in a vacuum at 50° C. for 18 hours to give 0.22 g (46%) of (Z)-2-(2-acetoxy-6-fluoro-1-indanylidene)acetamide as a white solid, mp 202°-203° C.; 1H-NMR (DMSO-d6): d 7.49 and 7.08 (d, 2H), 7.19-7.38 (m, 3H), 6.57 (s, 1H), 6.42 (d, 1H), 3.39 (dd, 1H, J=6.9 Hz, 17.7 Hz), and 2.82 (d, 1H, J=18.0 Hz), 1.91 (s, 3H); steady-state nOe: irradiation at 6.57 d, observed 22% nOe at 7.35 d.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][C:8]([O:11][Si](C(C)C)(C(C)C)C(C)C)=[CH:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[N-:22]=[N+:23]=[N-:24].[Na+].[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[Ce].O>C(#N)C>[N:22]([CH:7]1[C:8](=[O:11])[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6]1)=[N+:23]=[N-:24]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)[Si](OC1=CCC2(CC1)OCCO2)(C(C)C)C(C)C
Agent: [Ce]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: O=[N+]([O-])O
Product: [N-]=[N+]=NC1CC2(CCC1=O)OCCO2
Temperature: -20 °C
Reaction time: 4 h
Yield: 79.6 %

Procedure:
To a solution of (1,4-dioxaspiro[4.5]dec-7-en-8-yloxy) [tri(propan-2-yl)]silane (22.9 g) in acetonitrile (180 mL) were added dropwise sodium azide (21.4 g) and ammonium hexanitratocerate (IV) (121 g) at −20° C. The reaction mixture was stirred at −20° C. for 4 hr, ice-cooled water was added, and the mixture was extracted with diethyl ether. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (11.5 g).
Reaction SMILES: C[CH:2]([S:4](Cl)(=[O:6])=[O:5])C.[N:8]1[CH:9]=[CH:10][N:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][C:23]([CH:26]4[CH2:30][CH2:29][NH:28][CH2:27]4)=[CH:22][CH:21]=3)=[CH:13][C:12]=12.N1CC(C2C=CC(C(NCC3C=CN4C=CN=C4C=3)=O)=CC=2)C1>>[N:8]1[CH:9]=[CH:10][N:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19](=[O:31])[C:20]3[CH:21]=[CH:22][C:23]([CH:26]4[CH2:30][CH2:29][N:28]([S:4]([CH3:2])(=[O:6])=[O:5])[CH2:27]4)=[CH:24][CH:25]=3)=[CH:13][C:12]=12
Reactant: CC(C)S(=O)(=O)Cl
Reactant: O=C(NCc1ccn2ccnc2c1)c1ccc(C2CCNC2)cc1
Agent: O=C(NCc1ccn2ccnc2c1)c1ccc(C2CNC2)cc1
Product: CS(=O)(=O)N1CCC(c2ccc(C(=O)NCc3ccn4ccnc4c3)cc2)C1

Procedure:
The title compound was prepared as described in Example 557C, substituting methane sulfonyl chloride for propane-2-sulfonyl chloride and N-(imidazo[1,2-a]pyridin-7-ylmethyl)-4-(pyrrolidin-3-yl)benzamide for 4-(azetidin-3-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)benzamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (t, J=5.9 Hz, 1H), 8.48 (dd, J=6.9, 0.9 Hz, 1H), 7.88 (m, 3H), 7.52 (d, J=1.2 Hz, 1H), 7.45 (m, 2H), 7.38 (m, 1H), 6.85 (dd, J=6.9, 1.7 Hz, 1H), 4.51 (d, J=5.9 Hz, 2H), 3.73 (dd, J=9.6, 7.5 Hz, 1H), 3.47 (m, 2H), 3.35 (m, 1H), 3.19 (t, J=9.6 Hz, 1H), 2.97 (s, 3H), 2.31 (m, 1H), 2.02 (m, 1H); MS (ESI(+)) m/e 399 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:11])[C:5](=O)[CH2:6][C:7](=[O:9])[CH3:8])[CH3:2].Cl.[NH2:13]O.C(=O)([O-])O.[Na+]>C(O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:6]=[C:7]([CH3:8])[O:9][N:13]=1)=[O:11])[CH3:2]
Reactant: NO
Reactant: CCOC(=O)C(=O)CC(C)=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc(C)on1
Yield: 68 %

Procedure:
To a solution of ethyl-2,4-dioxovalerate (20 g, 126 mmol) in ethanol (85 mL), was added hydroxylamine hydrochloride (8.8 g, 126 mmol) and sodium hydrogen carbonate (10.6 g, 0.126 mmol). The reaction mixture was then heated under reflux for 1 hour. After cooling, the mixture was evaporated to leave a clear liquid that was distilled to leave the title compound as a colorless liquid (13.3 g, 68%); m/z (EI) 156.0 (MH).
Reaction SMILES: [Li+].[OH-].C[O:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[CH2:12][CH2:11][CH:10]2[N:16]1[C:24](=[O:25])[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[Cl:26])[CH2:17]1)=[O:6]>CO.O.CC(C)=O>[Cl:26][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:23]=1[C:24](=[O:25])[N:16]([CH:10]1[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([C:5]([OH:6])=[O:4])[CH:8]=3)[CH2:12][CH2:11]1)[CH2:17]2
Reactant: COC(=O)c1ccc2c(c1)C(N1Cc3cccc(Cl)c3C1=O)CC2
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: CC(C)=O
Product: O=C(O)c1ccc2c(c1)C(N1Cc3cccc(Cl)c3C1=O)CC2
Temperature: 25 °C
Reaction time: 72 h
Yield: 66 %

Procedure:
LiOH (5 equiv.) was added to a suspension of 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (D-01) (11.75 mmol) in methanol (90 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. for 72 h. Methanol was distilled off, the aqueous residue was acidified with 1N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01). Yield: 66%
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@@H:15]([CH2:16][C:17]#[N:18])[O:14][CH:11]([O:12][CH3:13])[C@@H:10]1OS(C(F)(F)F)(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.CSC.CO>C1CCCCC1>[CH2:1]([O:8][C@H:9]1[C@H:15]2[CH2:16][CH2:17][NH:18][C@@H:10]1[CH:11]([O:14]2)[O:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC1O[C@H](CC#N)[C@H](OCc2ccccc2)[C@H]1OS(=O)(=O)C(F)(F)F
Agent: B
Solvent: C1CCCCC1
Solvent: CSC
Solvent: CO
Product: COC1O[C@@H]2CCN[C@H]1[C@H]2OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.9 %

Procedure:
A 1:2 mixture of the α and β anomers of methyl 3-O-benzyl-5-cyano-5-deoxy-2-O-trifluoromethanesulphonyl-D-xylofuranoside (21αβ) (2.51 g, 6.36 mmol) dissolved in cyclohexane (200 ml) at 40° C. was treated with borane-dimethyl sulphide complex (10M in THF, 955 μl, 9.55 mmol) then stirred at room temperature overnight. Methanol (1 ml) was added, and the solvents evaporated then replaced with a 1:1 mixture of methanol and pyridine (50 ml). This was stirred with potassium carbonate (5 g) at room temperature for 48 hours. The solvents were removed and the residue dissolved in dichloromethane (20 ml), filtered and concentrated by evaporation. Purification using flash chromatography produced methyl 3-O-benzyl-2,6-imino-2,5,6-trideoxy-D-lyxohexofuranoside (α:β 1:2) (1.52 g, 96%) as a partially separated mixture of colourless oils which rapidly turn brown on storage.