Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C@@H:17]4[O:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]4)=[CH:16][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[ClH:30].CCOCC>O1CCOCC1>[ClH:30].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C@@H:17]4[O:22][CH2:21][CH2:20][NH:19][CH2:18]4)=[CH:16][C:10]=3[N:9]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCO[C@@H](c2ccc3[nH]c(-c4ccc(F)cc4)nc3c2)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Product: Fc1ccc(-c2nc3cc([C@H]4CNCCO4)ccc3[nH]2)cc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 76 %

Procedure:
(S)-tert-Butyl 2-(2-(4-fluorophenyl)-1H-benzo[d]imidazol-5-yl)morpholine-4-carboxylate (88 mg, 0.22 mmol) was dissolved in dioxane (1 ml) and a solution of HCl in dioxane (4M, 0.66 ml, 2.66 mmol) was added. The reaction mixture was stirred for 3 h at 60° C. After cooling ether (2 ml) was added and the solid was filtered off. It was washed with ether and dried in vacuo to afford (S)-2-(2-(4-fluorophenyl)-1H-benzo[d]imidazol-5-yl)morpholine hydrochloride (56 mg, 76%) as an off-white solid. MS (ISP): 298.2 ([M+H]+).
Reaction SMILES: N[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.N([O-])=O.[Na+].[BrH:18]>O>[Br:18][CH:2]([CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)[C:11]([OH:13])=[O:12]
Reactant: Br
Reactant: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=C(O)C(Br)Cc1ccc(O)cc1

Procedure:
Tyrosine (20 g) is dissolved in HBr (100 ml, 48% diluted with 200 ml water). To the cooled solution NaNO2 in 30 ml water is added dropwise. The product is extracted with ethyl acetate and after common treatment 2-bromo-3-(4-hydroxyphenyl)-propionic acid is obtained, which is used without purification for the next step.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]#[N:14])(C)(C)C.[ClH:16]>CCOCC>[ClH:16].[NH2:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]#[N:14]
Reactant: CC(C)(C)OC(=O)NCCOCCC#N
Agent: Cl
Solvent: CCOCC
Product: N#CCCOCCN

Procedure:
3-(2-Amino-ethoxy)-propionitrile hydrochloride (300 mg) was prepared by following General Procedure L starting from [2-(2-cyano-ethoxy)-ethyl]carbamic acid tert-butyl ester (430 mg) in 2M HCl in ether (2 mL).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH:10]=[C:9]2[CH:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18])[CH:5]=[CH:6][CH:7]=1.[B-](F)(F)(F)[F:28].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C(#N)C.O>>[F:28][C:10]1[C:11]2[C:12](=[N:13][CH:14]=[CH:15][CH:16]=2)[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[C:9]=1[CH:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18]
Reactant: CC(NC(=O)OC(C)(C)C)c1cc2cccnc2n1-c1cccc(F)c1
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Solvent: O
Product: CC(NC(=O)OC(C)(C)C)c1c(F)c2cccnc2n1-c1cccc(F)c1
Temperature: 50 °C
Yield: 15.3 %

Procedure:
A mixture of tert-butyl {1-[1-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]ethyl}carbamate (0.10 g, 0.28 mmol) and 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (0.10 g, 0.28 mmol) in acetonitrile (1.5 mL, 29 mmol) and water (0.15 mL, 8.3 mmol) was heated at 50° C. overnight. The reaction was cooled and extracted with dichloromethane. The combined organic layers were dried over MgSO4, concentrated and purified on silica gel (eluting with 0-20% EtOAc/hexane) to give the desired product (16 mg, 15%). LCMS calculated for C20H22F2N3O2(M+H)+: m/z=374.2. Found: 374.1.
Reaction SMILES: C([Si]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][O:18][CH3:19])[CH:11]=1)(C)C)(C)(C)C.C([Li])CCC.[CH3:25][C:26]([CH3:30])([CH3:29])[CH:27]=[O:28].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CCCCCC.C1COCC1.[Cl-].[NH4+]>[OH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH2:17][O:18][CH3:19])[C:11]=1[CH:27]([OH:28])[C:26]([CH3:30])([CH3:29])[CH3:25]
Reactant: CC(C)(C)C=O
Reactant: COCOc1cccc(CO[Si](C)(C)C(C)(C)C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COCOc1cccc(CO)c1C(O)C(C)(C)C
Reaction time: 2 h
Yield: 66.6 %

Procedure:
To a solution of tert-butyl-[[3-(methoxymethoxy)phenyl]methoxy]-dimethyl-silane (WO2012/076877 Intermediate 103, 500 mg, 1.77 mmol) in dry Hexane (5 mL), at room temperature, butyllithium 1.6M solution in Hexane (1.33 ml, 2.12 mmol) was slowly added and the reaction mixture was stirred for 2 hours at the same temperature. 2,2-dimethylpropanal (152.5 mg, 1.77 mmol) was added and the reaction mixture was stirred for further 30 minutes at the same temperature. The reaction was quenched with water (5 ml), diluted with an aqueous saturated solution of ammonium chloride (20 ml), and extracted with ethyl acetate (2×50 ml). The organic layer was dried (Na2SO4), filtered and evaporated. The residue was dissolved in THF (10 mL) and a 1M solution in THF of tetrabutylammonium fluoride (1.77 ml, 1.77 mmol) was added. The reaction mixture was stirred for 30 minutes at room temperature. The reaction was diluted with an aqueous saturated solution of ammonium chloride (20 ml), and extracted with ethyl acetate (2×50 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 25 g as column and cyclohexane/ethyl acetate from 100:0 to 70:30 as eluent affording the title compound (300 mg) as colorless oil.
Reaction SMILES: [N+](C1C=CC(C=O)=CC=1)([O-])=O.N1(C(OC(C)(C)C)=O)CCNCC1.C[C@H:26]1[CH2:31][N:30]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)[CH2:29][CH2:28][N:27]1[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]>>[N+:39]([C:36]1[CH:35]=[CH:34][C:33]([CH2:32][N:30]2[CH2:31][CH2:26][N:27]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:28][CH2:29]2)=[CH:38][CH:37]=1)([O-:41])=[O:40]
Reactant: C[C@H]1CN(Cc2ccc([N+](=O)[O-])cc2)CCN1C(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=Cc1ccc([N+](=O)[O-])cc1
Product: CC(C)(C)OC(=O)N1CCN(Cc2ccc([N+](=O)[O-])cc2)CC1

Procedure:
The title compound was prepared from 4-nitrobenzaldehyde and 1,1-dimethylethyl 1-piperazinecarboxylate using a method similar to that described for D1 in Description 1A although the product was purified by column chromatography followed by passing through an SCX column eluting with MeOH then 2M NH3 in MeOH. MS (ES+): 266.1, 222.2, no molecular ion (MH+) observed.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([S:18]([NH2:21])(=[O:20])=[O:19])=[CH:14][C:13]=1[N+:22]([O-:24])=[O:23].O>O1CCCC1>[N+:22]([C:13]1[CH:14]=[C:15]([S:18]([NH2:21])(=[O:19])=[O:20])[CH:16]=[CH:17][C:12]=1[O:8][CH2:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)([O-:24])=[O:23]
Reactant: OCC1CCOCC1
Reactant: NS(=O)(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: NS(=O)(=O)c1ccc(OCC2CCOCC2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
(Tetrahydro-2H-pyran-4-yl)methanol (2.0 g) in tetrahydrofuran (20 mL) was treated with 60% NaH (1.377 g). The mixture was stirred for 20 minutes at the room temperature. To this mixture was added 4-fluoro-3-nitrobenzenesulfonamide (2.84 g) portion-wise. The reaction was stirred for another 2 hours. The mixture was poured into water, neutralized with 10% HC1, and extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel eluting with 20%-60% ethyl acetate in hexanes.
Reaction SMILES: Cl[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH:12]([SH:15])([CH3:14])[CH3:13].[OH-].[Na+]>CS(C)=O.O>[CH:12]([S:15][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10])([CH3:14])[CH3:13]
Reactant: Nc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CC(C)S
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)Sc1ccc(N)cc1[N+](=O)[O-]
Reaction time: 72 h
Yield: 96.8 %

Procedure:
To a stirred solution containing 34.5 g (0.20 mole) of 4-chloro-3-nitroaniline and 24 g (0.30 mole) of isopropyl mercaptan in 200 ml of DMSO was added dropwise at ambient temperature a solution of 8.0 g (0.20 mole) of sodium hydroxide in 10 ml of water. The addition was exothermic to 60° and the mixture became deep red in color. After three days, the reaction mixture was poured into water and extracted with methylene chloride. The combined extracts were washed with water, dried with anhydrous MgSO4, filtered and concentrated to give 41.1 g (97%) of product as a red-brown syrup.
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:15]([N:17]1[C:23]2[N:24]=[CH:25][C:26]([CH2:28][CH2:29][OH:30])=[CH:27][C:22]=2[C:21](=[O:31])[N:20]([CH3:32])[C:19]2[CH:33]=[CH:34][CH:35]=[N:36][C:18]1=2)[CH3:16].O[C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:40][C:39]=1[CH3:52].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH2:15]([N:17]1[C:23]2[N:24]=[CH:25][C:26]([CH2:28][CH2:29][O:30][C:38]3[CH:43]=[CH:42][C:41]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[CH:40][C:39]=3[CH3:52])=[CH:27][C:22]=2[C:21](=[O:31])[N:20]([CH3:32])[C:19]2[CH:33]=[CH:34][CH:35]=[N:36][C:18]1=2)[CH3:16]
Reactant: CCN1c2ncc(CCO)cc2C(=O)N(C)c2cccnc21
Reactant: Cc1cc(NC(=O)OC(C)(C)C)ccc1O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCN1c2ncc(CCOc3ccc(NC(=O)OC(C)(C)C)cc3C)cc2C(=O)N(C)c2cccnc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 45.2 %

Procedure:
A solution of DIAD (258 μL, 1.31 mmol) in THF (4 mL) was added over 2 h to a solution of 11-ethyl-5,11-dihydro-8-(2-hydroxyethyl)-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (300 mg, 1.01 mmol), 1,1-dimethylethyl N-(4-hydroxy-3-methylphenyl)carbamate (225 mg, 1.01 mmol) and PPh3 (343 mg, 1.31 mmol) in THF (12 mL) at 25° C. The reaction mixture was stirred at 25° C. for 1 h. The mixture was concentrated under reduced pressure. The residue was purified by flash chromatography (Hexane:EtOAc, 7:3 to 1:1) to give the title compound (230 mg, 45% yield) as white solid.
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27](O)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:38][C@@H:39]1[C:70](=[O:71])[N:41]2[C:42]([C:54]([O:56][CH:57]([C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)=[O:55])=[C:43]([CH2:46][S:47][C:48]3[N:52]([CH3:53])[N:51]=[N:50][N:49]=3)[CH2:44][S:45][C@H:40]12.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31][CH:32]2[CH2:36][CH2:35][NH:34][C:33]2=[O:37])/[C:27]([NH:38][C@@H:39]2[C:70](=[O:71])[N:41]3[C:42]([C:54]([O:56][CH:57]([C:64]4[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=4)[C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)=[O:55])=[C:43]([CH2:46][S:47][C:48]4[N:52]([CH3:53])[N:51]=[N:50][N:49]=4)[CH2:44][S:45][C@H:40]23)=[O:28])[N:25]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: Cn1nnnc1SCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: O=C(O)/C(=N\OC1CCNC1=O)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Product: Cn1nnnc1SCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](NC(=O)/C(=N\OC3CCNC3=O)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)[C@H]2SC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59 %

Procedure:
3.25 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid are dissolved in 200 ml of tetrahydrofuran, and 3.14 g of benzhydryl 7β-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate, 1.03 g of 1-hydroxybenzotriazole and 1.57 g of dicyclohexylcarbodiimide are added thereto. The mixture is stirred at room temperature for 2 hours. Insoluble materials are filtered off, and the filtrate is concentrated to dryness under reduced pressure. The residue is dissolved in ethyl acetate, and washed with 1% hydrochloric acid, 5% aqueous sodium bicarbonate solution and an aqueous saturated sodium chloride solution, successively. The ethyl acetate solution is then dried and concentrated to dryness under reduced pressure. The residue thus obtained is purified by silica gel chromatography (solvent, ethyl acetate: benzene=5:2). 3.7 g of benzhydryl 7β-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] -3-cephem-4-carboxylate are obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][O:9][C:10]2[C:11]([C:16]3[CH:33]=[CH:32][C:19]4[CH2:20][CH2:21][N:22](C(OC(C)(C)C)=O)[CH2:23][CH2:24][C:18]=4[CH:17]=3)=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:3]=1.Cl>O1CCOCC1>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][O:9][C:10]2[C:11]([C:16]3[CH:33]=[CH:32][C:19]4[CH2:20][CH2:21][NH:22][CH2:23][CH2:24][C:18]=4[CH:17]=3)=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:3]=1
Reactant: Cc1ccnc(COc2cccnc2-c2ccc3c(c2)CCN(C(=O)OC(C)(C)C)CC3)c1
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ccnc(COc2cccnc2-c2ccc3c(c2)CCNCC3)c1

Procedure:
1,1-dimethylethyl 7-(3-{[(4-methyl-2-pyridinyl)methyl]oxy}-2-pyridinyl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (3.8 g) was dissolved in dioxane (20 ml). Gaseous hydrogen chloride was passed through the reaction mixture for 1.5 h. The reaction was monitored by TLC. On completion the solid formed was collected by filtration and washed with acetone. The solid was then dissolved in water and the mixture neutralised with aqueous sodium hydroxide (1M). The sticky solid formed was extracted with DCM. The organic phase was dried over sodium sulphate and concentrated in vacuo to give a solid. This was purified through silica, eluting the product with 0-12% methanol in DCM. The solid from this was triturated in diethyl ether to give the title compound, 2 g (69%) yield.
Reaction SMILES: Br.Cl[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH3:16])[S:14][CH:15]=2)=[CH:7][CH:6]=1.Cl.[F:18][C:19]([F:33])([F:32])[C:20]1[CH:21]=[C:22]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:23]=[CH:24][CH:25]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+]>CC(CC(C)C)=O>[F:33][C:19]([F:18])([F:32])[C:20]1[CH:21]=[C:22]([N:26]2[CH2:31][CH2:30][N:29]([CH2:3][CH2:4][C:5]3[CH:10]=[CH:9][C:8]([C:11]4[N:12]=[C:13]([CH3:16])[S:14][CH:15]=4)=[CH:7][CH:6]=3)[CH2:28][CH2:27]2)[CH:23]=[CH:24][CH:25]=1
Reactant: FC(F)(F)c1cccc(N2CCNCC2)c1
Reactant: Cc1nc(-c2ccc(CCCl)cc2)cs1
Agent: Br
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC(=O)CC(C)C
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(-c2ccc(CCN3CCN(c4cccc(C(F)(F)F)c4)CC3)cc2)cs1

Procedure:
To a 125 ml round-bottomed flask equipped with condenser and N2 inlet were added 2.39 g (7.5 mmol) of 4-(4-(2-chloroethyl)phenyl)-2-methylthiazole hydrobromide, 2.0 g (7.5 mmol) of N-(3-trifluoromethylphenyl)piperazine hydrochloride, 2.62 ml (15.0 mmol) of diisopropylethylamine, 1.59 g (15.0 mmol) of sodium carbonate, 5 mg of sodium iodide, and 50 ml of methylisobutylketone. The reaction was heated at reflux for 4.5 days, filtered hot to remove inorganic material, cooled, and the precipitate filtered and washed with ether and ethyl acetate. The solid was taken up in methylene chloride, hydrochloride gas bubbled through to precipitate the salt, and the resulting solid filtered, washed with methylene chloride, and dried to give a solid, m.p. 170°-175° C., 1.93 g (51%).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13]3[CH:16]=[C:17]([O:20][CH2:21][CH2:22][NH:23][OH:24])[CH:18]=[CH:19][C:12]=3[S:11]2(=[O:26])=[O:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N:31]=[C:32]=[O:33])(C)C>>[C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13]3[CH:16]=[C:17]([O:20][CH2:21][CH2:22][N:23]([C:32]([NH2:31])=[O:33])[OH:24])[CH:18]=[CH:19][C:12]=3[S:11]2(=[O:25])=[O:26])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S1(=O)c2ccc(OCCNO)cc2CCN1CCCc1ccccc1
Reactant: C[Si](C)(C)N=C=O
Product: NC(=O)N(O)CCOc1ccc2c(c1)CCN(CCCc1ccccc1)S2(=O)=O

Procedure:
Similarly to procedure described in example 1, 2-(3-phenylpropyl)-6-[2-(N-hydroxyamino)-ethoxy]-3,4-dihydro-2H-1,2-benzothiazine-1,1-dioxide is reacted with trimethylsilyl isocyanate to yield 2-(3-phenylpropyl)-6-[2-(N-aminocarbonyl-N-hydroxyamino)-ethoxy]-3,4-dihydro-2H-1,2-benzothiazine-1,1-dioxide, m.p. 134°-135°.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23](O)=[O:24])=[C:16]2[C:15]=1[F:26].[NH2:27][CH:28]1[CH2:33][CH2:32][C:31]([CH2:35][OH:36])([OH:34])[CH2:30][CH2:29]1.[Cl-].[NH4+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23]([NH:27][CH:28]3[CH2:33][CH2:32][C:31]([OH:34])([CH2:35][OH:36])[CH2:30][CH2:29]3)=[O:24])=[C:16]2[C:15]=1[F:26]
Reactant: NC1CCC(O)(CO)CC1
Reactant: O=C(O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)c(F)c12
Agent: [Cl-]
Agent: [NH4+]
Product: O=C(NC1CCC(O)(CO)CC1)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)c(F)c12

Procedure:
The title compound was prepared by the method similar to that mentioned in Example-6, using (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-4-fluoropyrazolo[1,5-a]pyridine-3-carboxylic acid and 4-amino-1-(hydroxymethyl)cyclohexanol (instead of ammonium chloride) to afford the crude compound. The crude compound was purified by Preparative TLC (using Silicagel GF254, 1000 u coated 20×20 cm dimension glass plate and 100% EtOAc as eluent) to afford 15 mg of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[CH2:19]([N:21]1[C:25]([CH2:26]O)=[CH:24][C:23]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[N:22]1)[CH3:20].CN(C)C(N=NC(N(C)C)=O)=O.C(P(CCCC)CCCC)CCC>>[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:26][C:25]3[N:21]([CH2:19][CH3:20])[N:22]=[C:23]([C:28]4[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:32][CH:33]=4)[CH:24]=3)[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCn1nc(-c2ccc(C(F)(F)F)cc2)cc1CO
Reactant: CC(C)(C)OC(=O)Cn1ccc2ccc(O)cc21
Agent: CCCCP(CCCC)CCCC
Agent: CN(C)C(=O)N=NC(=O)N(C)C
Product: CCn1nc(-c2ccc(C(F)(F)F)cc2)cc1COc1ccc2ccn(CC(=O)OC(C)(C)C)c2c1

Procedure:
In analogy to the procedure described for example 3 c], (6-hydroxy-indol-1-yl)-acetic acid tert-butyl ester (example 1 d]) was reacted with [2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-yl]-methanol in the presence of N,N,N′,N′-tetramethyl azodicarboxamide and tributylphosphine to give {6-[2-ethyl-5-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-ylmethoxy]-indol-1-yl}-acetic acid tert-butyl ester as colorless oil.
Reaction SMILES: [Cl-].[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([CH2:21][C@H:22]([NH3+:27])[C:23]([O:25][CH3:26])=[O:24])[CH:13]=[CH:14][C:15]=1[O:16][C:17](=[O:20])[NH:18][CH3:19])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH2:35]([O:42][C:43]([NH:45][C@@H:46]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[C:53]([O:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[CH:52]=1)[C:47](O)=[O:48])=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1C=CC2N(O)N=NC=2C=1>ClCCl.C(Cl)CCl>[CH3:26][O:25][C:23](=[O:24])[C@@H:22]([NH:27][C:47](=[O:48])[C@@H:46]([NH:45][C:43]([O:42][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:44])[CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH2:58][C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)=[C:53]([O:65][CH2:66][C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)[CH:52]=1)[CH2:21][C:12]1[CH:13]=[CH:14][C:15]([O:16][C:17](=[O:20])[NH:18][CH3:19])=[C:10]([O:9][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:11]=1
Reactant: CNC(=O)Oc1ccc(C[C@H]([NH3+])C(=O)OC)cc1OCc1ccccc1
Reactant: O=C(N[C@@H](Cc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1)C(=O)O)OCc1ccccc1
Agent: On1nnc2ccccc21
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClCCCl
Product: CNC(=O)Oc1ccc(C[C@H](NC(=O)[C@H](Cc2ccc(OCc3ccccc3)c(OCc3ccccc3)c2)NC(=O)OCc2ccccc2)C(=O)OC)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
(S)-2-(3-Benzyloxy-4-methylcarbamoyloxy-phenyl)-1-methoxycarbonyl-ethyl-ammonium chloride was suspended in dichloromethane (20 ml), then triethylamine (0.18 g) was added, followed by the addition of (S)-2-benzyloxycarbonylamino-3-(3,4-bis-benzyloxy-phenyl)-propionic acid (0.85 g), [see German patent DE 2121187], and HOBt (0.25 g). The mixture was stirred at room temperature for 20 min. EDC (0.35 g) was added and stirring was continued overnight. The mixture was washed with sodium bicarbonate, dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel chromatography eluting with ethyl acetate/dichloromethane (1:2). (S)-2-[(S)-2-Benzyloxycarbonylamino-3-(3,4-bis-benzyloxy-phenyl)-propionylamino]-3-(3-benzyloxy-4-methylcarbamoyloxy-phenyl)-propionic acid methyl ester was obtained as a white solid, 1.25 g. 1H NMR (400 MHz, CDCl3) 2.63 (d, J=4.6 Hz, 3H), 2.87-3.06 (m, 4H), 3.56 (s, 3H), 4.28-4.34 (m, 1H), 4.53-4.58 (m, 1H), 4.86-5.09 (m, 8H), 6.78 (m, 2H), 6.95 (m, 2H), 7.09 (m, 2H), 7.20-7.54 (m, 22H), 8.51 (m, 1H).
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:4].[CH3:25][C:26]1[CH:27]=[C:28]([N:32]=[C:33]=[O:34])[CH:29]=[CH:30][CH:31]=1>>[CH2:15]([O:14][C:12]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[N:5]([CH2:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[C:3](=[O:4])[CH2:2][NH:1][C:33]([NH:32][C:28]1[CH:29]=[CH:30][CH:31]=[C:26]([CH3:25])[CH:27]=1)=[O:34])=[O:13])[CH3:16]
Reactant: Cc1cccc(N=C=O)c1
Reactant: CCOC(=O)c1ccccc1N(CC(=O)OC(C)(C)C)C(=O)CN
Product: CCOC(=O)c1ccccc1N(CC(=O)OC(C)(C)C)C(=O)CNC(=O)Nc1cccc(C)c1
Yield: 27 %

Procedure:
Using a procedure similar to that described in Example 1, but starting with tert-butyl 2-[2-amino-N-(2-ethoxycarbonylphenyl)acetamido]acetate (3.6 g) and 3-methylphenyl isocyanate (1.42 g), and after recrystallisation in diisopropyl ether, tert-butyl 2-{N-(2-ethoxycarbonylphenyl)-2-[3-(3-methylphenyl)ureido]acetamido}acetate (1.35 g), m.p. 142° C., is obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([CH2:13][OH:14])[N:12]=2)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([CH:13]=[O:14])[N:12]=2)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1
Reactant: Cc1ccc(-c2nc(CO)cs2)c([N+](=O)[O-])c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: Cc1ccc(-c2nc(C=O)cs2)c([N+](=O)[O-])c1
Reaction time: 0.5 h

Procedure:
2-(4-Methyl-2-nitro phenyl)thiazol-4-yl methanol (297 mg, 1.18 mmol) was stirred in 5 mL of CH2Cl2 at room temperature under N2. The Dess-Martin reagent (500 mg, 1.18 mmol) was added as a solid. After 30 minutes, the reaction was complete. The reaction was diluted to 60 mL of CH2Cl2 and washed with 60 mL of 1N NaOH. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified on a biotage column 12M eluted with EtOAc/hexanes 1:4 to give the desired material.