Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[CH:7][C:6]=1[CH3:20])=O.[NH2:21][C:22]([NH2:24])=[S:23]>CCO>[F:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][C:8]2[CH:9]=[C:10]([CH3:11])[C:5]([C:3]3[N:21]=[C:22]([NH2:24])[S:23][CH:2]=3)=[C:6]([CH3:20])[CH:7]=2)=[CH:14][CH:15]=1
Reactant: NC(N)=S
Reactant: Cc1cc(Oc2ccc(F)cc2)cc(C)c1C(=O)CBr
Solvent: CCO
Product: Cc1cc(Oc2ccc(F)cc2)cc(C)c1-c1csc(N)n1
Yield: 84.2 %

Procedure:
A mixture of 2-bromo-1-(4-(4-fluorophenoxy)-2,6-dimethylphenyl)ethanone (5.74 g, 17.0 mmol) and thiourea (1.30 g, 17.1 mmol) in 95% EtOH (24.3 mL) was heated at reflux for 60 min. The solution was concentrated and added with water (100 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene. The solids were filtered and dried under vacuum to give 4-(4-(4-fluorophenoxy)-2,6-dimethylphenyl)thiazol-2-amine (4.50 g) as yellow solids in 84% yield: 1H NMR (500 MHz, CDCl3) δ 7.05-6.97 (m, 4 H), 6.66 (s, 2 H), 6.28 (s, 1 H), 5.95 (bs, 2 H), 2.14 (s, 6 H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]3[C:17]4[C:22]([CH:23]=[CH:24][C:9]2=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:4][CH:3]=1.O=C1CC(=O)N(C2C=CC(C(OCC)=O)=CC=2)C2C=CC3C(C=2N1)=CC=CC=3.[Cl:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[CH2:60][CH2:61][C:62](Cl)=[O:63].O=C1CC(=O)N(C2C=CC(C(O)=O)=CC=2)C2C=CC3C(C=2N1)=CC=CC=3>>[Cl:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[CH2:60][CH2:61][C:62]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]3[C:17]4[C:22]([CH:23]=[CH:24][C:9]2=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:4][CH:3]=1)=[O:63]
Reactant: Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Reactant: O=C(Cl)CCc1ccccc1Cl
Agent: CCOC(=O)c1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Agent: O=C1CC(=O)N(c2ccc(C(=O)O)cc2)c2ccc3ccccc3c2N1
Product: O=C(CCc1ccccc1Cl)Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Yield: 56 %

Procedure:
By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3) (35 mg, 0.110 mmol), and 3-(2-chlorophenyl)propionic acid chloride (0.132 mmol), the title compound (30 mg, yield 56%) was obtained as white crystals in the same manner as that of Example 1, (4).
Reaction SMILES: [CH:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH2:11]([O:15][C:16](=[O:20])[C@H:17]([CH3:19])[NH2:18])[CH:12]([CH3:14])[CH3:13]>>[CH2:11]([O:15][C:16](=[O:20])[C@H:17]([CH3:19])[NH:18][C:7](=[O:9])[CH2:6][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)[CH:12]([CH3:14])[CH3:13]
Reactant: CC(C)COC(=O)[C@H](C)N
Reactant: O=C(O)CC1CCCC1
Agent: Cl
Product: CC(C)COC(=O)[C@H](C)NC(=O)CC1CCCC1

Procedure:
Following General Procedure B′ above, and using cyclopentylacetic acid (Aldrich) and L-alanine iso-butyl ester hydrochloride (from Example B′ above), the title compound was prepared as a solid having a melting point of 62° C.-64° C. The reaction was monitored by tlc on silica gel (Rf=0.37 in 1:3 EtOAc:hexane) and purification was by extraction with Et2O followed by washes with aqueous K2CO3 and aqueous HCl.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH2:10][CH:9]([NH2:11])[CH2:8][CH2:7][C:5]=2[N:6]=1.[CH:12](=O)[CH2:13][CH2:14][CH3:15].[BH4-].[Na+].[ClH:19]>CN(C)C=O.O>[ClH:19].[ClH:19].[NH2:1][C:2]1[S:3][C:4]2[CH2:10][CH:9]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:8][CH2:7][C:5]=2[N:6]=1
Reactant: Nc1nc2c(s1)CC(N)CC2
Reactant: CCCC=O
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCNC1CCc2nc(N)sc2C1
Temperature: 50 °C

Procedure:
To a solution of 3.4 g (0.02 Mol) of 2,6-diamino- 4,5,6,7-tetrahydro-benzthiazole in 34 ml of dimethylformamide are added 1.8 g (0.022 Mol) of n- butanal and the mixture is heated to 50° C. for 1 hour. After cooling, the reaction solution is mixed with 0.8 g (0.02 Mol) of sodium borohydride and heated to 50° C. for 30 minutes. The solvent is largely eliminated in vacuo. Whilst cooling with ice, the residue is mixed with 20 ml of water and 2N hydrochloric acid until a pH of 1 is obtained. The aqueous solution is extracted with ethylacetate and the organic phase discarded. The aqueous phase is mixed with potassium carbonate until an alkaline reaction is obtained and then extracted with ethyl acetate. The organic phase is dried and concentrated. The compound crystallizes out when ethereal hydrochloric acid is added.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([O:21][C:22](=[O:26])[CH2:23][CH2:24][NH2:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH2:14]([O:21][C:22](=[O:26])[CH2:23][CH2:24][NH:25][C:11](=[O:13])[CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NCCC(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)NCCC(=O)O
Product: CC(C)(C)OC(=O)NCCC(=O)NCCC(=O)OCc1ccccc1

Procedure:
N-(t-butoxycarbonyl)-β-alanine and β-alanine benzyl ester were coupled analogously to the above examples to give N-[N-(t-butoxycarbonyl)-β-alanyl]-β-alanine benzyl ester, mp. 84°-85° C.
Reaction SMILES: [Br:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]=[CH:7][N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:13][N:14]([CH3:18])[C:15](=[S:17])[S-:16].C[NH2+]C>C(=S)=S>[CH3:13][N:14]([CH3:18])[C:15](=[S:16])[S:17][CH:6]([CH2:7][N+:8]([O-:10])=[O:9])[C:5]1[CH:11]=[CH:12][C:2]([Br:1])=[CH:3][CH:4]=1
Reactant: O=[N+]([O-])C=Cc1ccc(Br)cc1
Reactant: CN(C)C(=S)[S-]
Agent: C[NH2+]C
Solvent: S=C=S
Product: CN(C)C(=S)SC(C[N+](=O)[O-])c1ccc(Br)cc1

Procedure:
As in Example 17, reaction of p-bromo-β-nitrostyrene with dimethylammonium dimethyldithiocarbamate in the presence of carbon disulfide gave p-bromo-α-(nitromethyl)benzyl dimethyldithiocarbamate melting at 79° - 81° C. when recrystallized without heating from acetone-ethanol solution.
Reaction SMILES: [CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([N:10]3[CH2:14][CH2:13][C:12]4([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]4)[C:11]3=[O:20])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.S(Cl)([Cl:24])(=O)=O.CCN(CC)CC>C(Cl)(Cl)Cl>[Cl:24][C:6]1[CH:5]=[C:4]([CH:1]2[CH2:3][CH2:2]2)[CH:9]=[CH:8][C:7]=1[N:10]1[CH2:14][CH2:13][C:12]2([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[C:11]1=[O:20]
Reactant: O=C1N(c2ccc(C3CC3)cc2)CCC12CCNCC2
Reactant: O=S(=O)(Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C1N(c2ccc(C3CC3)cc2Cl)CCC12CCNCC2
Yield: 30.8 %

Procedure:
A mixture of 0.275 g (1 mmol) 2-(4-Cyclopropyl-phenyl)-2,8-diaza-spiro[4.5]decan-1-one. 1.57 g (11.3 mmol) sulfuryl chloride and 0.154 g (1.52 mmol) NEt3 in 50 mL CHCl3 was stirred at room temperature. After evaporation of the volatiles the residue was taken up in DMF and subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 94 mg (30%) of the title compound as light yellow gum. MS m/e: 305.1 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1([NH2:23])[NH:11][C:10](=[O:12])[C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=3)[N:8]=2)[NH:3]1.[C:24](OC(=O)C)(=[O:26])[CH3:25]>C(O)(=O)C>[C:24]([NH:23][C:2]1([NH2:1])[NH:11][C:10](=[O:12])[C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=3)[N:8]=2)[NH:3]1)(=[O:26])[CH3:25]
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(N)N3)cc1OC
Solvent: CC(=O)O
Product: COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC
Yield: 77 %

Procedure:
A suspension of the compound of example 48 (10.46 g, 35 mmoles) in acetic anhydride (600 ml) and acetic acid (200 ml) was refluxed for 1 hour until a clear solution was formed. By cooling down the reaction mixture in the refrigerator, the precipitate formed was filtered off, washed with ethyl acetate and diethyl ether, and then dried over P2O5 under vacuum, providing the title compound as a yellow powder (9.19 g, yield: 77%). This compound was further characterized by the following spectra:
Reaction SMILES: [CH3:1][N:2]1[C:11]2[CH:10]=[C:9]([CH:12]=C)[CH:8]=[CH:7][C:6]=2[C:5]2=[N:14][O:15][C:16]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])=[C:4]2[CH2:3]1.[O:32]=[O+][O-].C(N(CC)CC)C>ClCCl>[CH3:1][N:2]1[C:11]2[CH:10]=[C:9]([CH:12]=[O:32])[CH:8]=[CH:7][C:6]=2[C:5]2=[N:14][O:15][C:16]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])=[C:4]2[CH2:3]1
Reactant: C=Cc1ccc2c(c1)N(C)Cc1c-2noc1-c1onc(-c2ccccc2)c1C(F)(F)F
Reactant: O=[O+][O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1Cc2c(noc2-c2onc(-c3ccccc3)c2C(F)(F)F)-c2ccc(C=O)cc21
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of 5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydroisoxazolo[4,3-c]quinoline (Preparation 77F, 0.020 g, 0.047 mmol) in Dichloromethane (5 mL) at −78° C. was passed ozone from an ozone generator until the solution turned a deep blue. The reaction mixture then was purged with oxygen until the blue color disappeared, then with nitrogen for five minutes. The reaction mixture was allowed to warm to room temperature and triethylamine (5.07 μl, 0.036 mmol) was added. The reaction mixture was stirred at room temperature for fifteen minutes, and then concentrated under vacuum to give 5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydroisoxazolo[4,3-c]quinoline-7-carbaldehyde as a tan solid. (0.015 mg, 0.035 mmol, 74%). The product had an HPLC ret. time=3.61 min. (condition B). LC/MS M+1=426.1 min
Reaction SMILES: [CH:1]1([CH2:6][C:7](Cl)=[O:8])[CH2:5]CC[CH2:2]1.[C:10]([C:12]1[CH:36]=[CH:35][C:15]([CH2:16][NH:17][C:18]2[S:19][C:20]([C:23]([NH:25][C:26]3[CH:27]=[CH:28][C:29]4[N:30]([CH:32]=[CH:33][N:34]=4)[CH:31]=3)=[O:24])=[CH:21][N:22]=2)=[CH:14][CH:13]=1)#[N:11].NC1C=CC(C(OC)=O)=CC=1>>[C:10]([C:12]1[CH:13]=[CH:14][C:15]([CH2:16][N:17]([C:7](=[O:8])[CH2:6][CH:1]([CH3:5])[CH3:2])[C:18]2[S:19][C:20]([C:23]([NH:25][C:26]3[CH:27]=[CH:28][C:29]4[N:30]([CH:32]=[CH:33][N:34]=4)[CH:31]=3)=[O:24])=[CH:21][N:22]=2)=[CH:35][CH:36]=1)#[N:11]
Reactant: N#Cc1ccc(CNc2ncc(C(=O)Nc3ccc4nccn4c3)s2)cc1
Reactant: O=C(Cl)CC1CCCC1
Agent: COC(=O)c1ccc(N)cc1
Product: CC(C)CC(=O)N(Cc1ccc(C#N)cc1)c1ncc(C(=O)Nc2ccc3nccn3c2)s1

Procedure:
The title compound was prepared as described in Example 52A, substituting 3-methylbutanoyl chloride for 2-cyclopentylacetyl chloride and 2-(4-cyanobenzylamino)-N-(imidazo[1,2-a]pyridin-6-yl)thiazole-5-carboxamide for methyl 4-aminobenzoate. 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H), 9.62 (s, 1H), 8.43 (d, J=1.6 Hz, 1H), 8.32 (s, 1H), 8.11 (s, 1H), 7.99-7.89 (m, 2H), 7.82 (dd, J=18.8, 8.3 Hz, 2H), 7.38 (d, J=8.3 Hz, 2H), 5.63 (s, 2H), 2.14 (dt, J=13.4, 6.7 Hz, 1H), 0.88 (d, J=6.7 Hz, 6H); (APCI(+)) m/e 459 (M+H)+.
Reaction SMILES: S([O-])(O[O-])(=O)=[O:2].[K+].[K+].[N+:9]([CH2:12][S:13][C:14]1[C:19]2[O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:18]=2[CH:17]=[CH:16][CH:15]=1)([O-:11])=[O:10]>O.COCCOC>[N+:9]([CH2:12][S:13]([C:14]1[C:19]2[O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:18]=2[CH:17]=[CH:16][CH:15]=1)=[O:2])([O-:11])=[O:10]
Reactant: O=S(=O)([O-])O[O-]
Reactant: O=[N+]([O-])CSc1cccc2c1oc1ccccc12
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: O=[N+]([O-])CS(=O)c1cccc2c1oc1ccccc12
Reaction time: 18 h
Yield: 98.4 %

Procedure:
A solution of potassium peroxymonosulphate (`Oxone`, trade mark; 12.8 g, 20.8 mmol) in water (52 ml) was added in one portion to a stirred solution of the nitromethylthio derivative (C) (3.64 g, 14.1 mmol) in 1,2-dimethoxyethane (75 ml). The mixture was stirred vigorously for 18 hours. The reaction mixture was diluted with water (300 ml). The solid obtained was collected by filtration, air dried and recrystallised from toluene to give 4-(nitromethylsulphinyl)dibenzofuran as a white solid (3.82 g), m.p. 174°-176° C.; microanalysis found: C,56.8; H,3.2; N,5.0%; C13H9NO4S requires: C,56.7; H,3.3 N,5.1%.
Reaction SMILES: [OH:1][C:2]1[C:3]2[N:4]([C:8]([CH2:12][OH:13])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].Cl[CH2:23][C:24]1[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][C:25]=1[NH:31][C:32](=[O:38])[O:33][CH2:34][CH2:35][O:36][CH3:37]>CC(C)=O>[CH3:37][O:36][CH2:35][CH2:34][O:33][C:32]([NH:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:24]=1[CH2:23][O:1][C:2]1[C:3]2[N:4]([C:8]([CH2:12][OH:13])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:38]
Reactant: COCCOC(=O)Nc1cccc(C)c1CCl
Reactant: Cc1nc2c(O)cccn2c1CO
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COCCOC(=O)Nc1cccc(C)c1COc1cccn2c(CO)c(C)nc12
Temperature: 25 °C
Reaction time: 48 h
Yield: 61.8 %

Procedure:
A mixture of 178 mg (1.0 mmol) of 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-methanol, 117 mg (1.1 mmol) of anhydrous sodium carbonate, 15 mg (0.1 mmol) of sodium iodide and 283 mg (1.1 mmol) of 2-methoxyethyl 2-chloromethyl-3-methylphenylcarbamate in 5 ml of acetone is stirred at RT for 48 h, worked up analogously to Example 2 and chromatographed by means of ethyl acetate/isopropyl alcohol (9:1). 247 mg (62%) of the title compound are obtained.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[CH3:10].C(#N)C.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>O>[CH:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:3]([CH3:10])[CH:4]=1)=[O:7]
Reactant: Cc1cc(C=O)ccc1O
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)COc1ccc(C=O)cc1C
Reaction time: 16 h
Yield: 88 %

Procedure:
To a solution of 4-hydroxy-3-methylbenzaldehyde (8 g, 58.8 mmol) in an hydrous acetonitrile (300 mL), under nitrogen at 0° C., was added caesium carbonate (21 g, 64.6 mmol) and ethyl bromoacetate (6.52 mL, 58.8 mmol). The resulting mixture was allowed to come to room temperature and stirred for 16 h. The reaction mixture was diluted with water (400 mL) and extracted with EtOAc (2×500 mL). The combined organic extracts were dried (MgSO4) and the solvents removed in vacuo, to afford the title compound as brown solid (11.5 g).
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]([OH:10])[C:7]([OH:9])=[O:8])=[CH:4][CH:3]=1.CC(N(C)C)=O.CC(C)([O-])C.[K+].[N+:25]([C:28]1[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=1)([O-:27])=[O:26]>C(OCC)(=O)C>[OH:1][C:2]1[CH:12]=[CH:11][C:5]([CH:6]([OH:10])[C:7]([O:9][CH2:32][C:31]2[CH:34]=[CH:35][C:28]([N+:25]([O-:27])=[O:26])=[CH:29][CH:30]=2)=[O:8])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Reactant: O=C(O)C(O)c1ccc(O)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: O=C(OCc1ccc([N+](=O)[O-])cc1)C(O)c1ccc(O)cc1
Temperature: 25 °C
Yield: 84 %

Procedure:
To a solution of 16.8 g. (0.1 mole) of 4-hydroxymandelic acid in 300 ml. of dimethylacetamide were added 11.2 g. of potassium t-butoxide with an additional 100 ml. of dimethylacetamide. The mixture was stirred at room temperature until a solution was obtained. p-Nitrobenzyl bromide (21.6 g., 0.1 mole) was added to the solution followed by 100 ml. of additional dimethylacetamide. The reaction mixture was stirred for 24 hours and was diluted with one liter of ethyl acetate. The mixture was washed repeatedly with water and dried over magnesium sulfate. The dried solution was evaporated to yield 25 g. (84 percent yield) of p-nitrobenzyl 4-hydroxymandelate.
Reaction SMILES: C([O:5][C:6](=O)[CH2:7][N:8]1[C:13]2[CH:14]=[C:15]([C:18]([O:20]CC)=[O:19])[CH:16]=[CH:17][C:12]=2[S:11][C@H:10]([CH2:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:9]1=[O:34])(C)(C)C.BrC1C=C(C(OCC)=O)C=CC=1S[C@@H](CCCC1C=CC(OC)=CC=1)C(O)=O.CC1(C)C23[C@@]4([O:79][N:74]4S(=O)(=O)C2)C(Cl)(Cl)[C@H]1CC3>C(OCC)(=O)C>[OH:79][NH:74][C:6](=[O:5])[CH2:7][N:8]1[C:13]2[CH:14]=[C:15]([C:18]([OH:20])=[O:19])[CH:16]=[CH:17][C:12]=2[S:11][CH:10]([CH2:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:9]1=[O:34]
Reactant: CC1(C)[C@@H]2CCC13CS(=O)(=O)N1O[C@]13C2(Cl)Cl
Reactant: CCOC(=O)c1ccc2c(c1)N(CC(=O)OC(C)(C)C)C(=O)[C@@H](CCCc1ccc(OC)cc1)S2
Agent: CCOC(=O)c1ccc(S[C@@H](CCCc2ccc(OC)cc2)C(=O)O)c(Br)c1
Solvent: CCOC(C)=O
Product: COc1ccc(CCCC2Sc3ccc(C(=O)O)cc3N(CC(=O)NO)C2=O)cc1

Procedure:
The compound of Example 14 (25% and 90% e.e.) was obtained by the same process as described in Reference Example 14, except for using the compound of Example 8, (+)-(8,8-dichlorocamphorylsulfonyl)oxaziridine and ethyl acetate as solvent. The optical purity was determined by the method described in Example 14.
Reaction SMILES: C(Cl)(Cl)Cl.[SH:5][C:6]1[C:7]([NH:16][C:17]([C:19]2([CH2:25][CH:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])=[CH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2.[C:31](Cl)(=[O:35])[CH:32]([CH3:34])[CH3:33]>N1C=CC=CC=1>[CH2:27]([CH:26]([CH2:29][CH3:30])[CH2:25][C:19]1([C:17]([NH:16][C:7]2[C:6]([S:5][C:31](=[O:35])[CH:32]([CH3:34])[CH3:33])=[CH:15][C:14]3[C:9]([CH:8]=2)=[CH:10][CH:11]=[CH:12][CH:13]=3)=[O:18])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1)[CH3:28]
Reactant: CC(C)C(=O)Cl
Reactant: CCC(CC)CC1(C(=O)Nc2cc3ccccc3cc2S)CCCCC1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CCC(CC)CC1(C(=O)Nc2cc3ccccc3cc2SC(=O)C(C)C)CCCCC1
Reaction time: 1 h

Procedure:
To a chloroform solution of the product obtained in step B) are added 1.05 mol equivalents of isobutyryl chloride and 2.5 mol equivalents of pyridine at room temperature. The mixture is stirred for 1 hour, concentrated and then n-hexane is added. The solids are filtered off and the filtrate is concentrated. The remaining residue is purified by silica gel column chromatography to obtain the desired title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:24]([CH:25]=[O:26])=[C:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[S:22][N:21]=2)=[CH:16][CH:15]=1>CCOCC.C1COCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[C:24]([CH:25]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=3)[OH:26])=[C:23]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[S:22][N:21]=2)=[CH:18][CH:19]=1
Reactant: O=Cc1c(-c2ccc(Cl)cc2)nsc1-c1ccccc1
Reactant: Brc1cccnc1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: OC(c1cccnc1)c1c(-c2ccc(Cl)cc2)nsc1-c1ccccc1
Reaction time: 0.25 h
Yield: 105.5 %

Procedure:
A solution of 3-bromopyridine (103 mg) in 2.5 ml of ether is cooled to −78° C. under N2 and to this is added drop-wise a BuLi solution (0.375 ml, 1.6 M in hex). After stirring for 15 min, a solution of 15 (150 mg) in THF is added drop-wise. Stirring is continued for 20 min at −78° C., the red colored reaction mixture is quenched with water (5 ml) and the cooling bath is removed. Water (25 ml) and EtOAc (30 ml) are added. After washing, the layers are separated, the organic layer is washed with brine, dried and concentrated to afford an orange foam (200 mg). The material is purified by flash column chromatography (2% MeOH in CH2Cl2). Desired compound 16 is obtained as white foam showing the expected mass in LCMS (M+1:379 and its isotopes at 380; 381 and 382).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10]C)[CH:7]=[CH:6][C:4]=1[NH2:5].[F:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22]C)C(O)=O>>[F:12][C:13]1[CH:14]=[C:15]([C:1]2[O:2][C:3]3[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:4]=3[N:5]=2)[CH:19]=[CH:20][C:21]=1[OH:22]
Reactant: COc1ccc(C(=O)O)cc1F
Reactant: COc1ccc(N)c(OC)c1
Product: Oc1ccc2nc(-c3ccc(O)c(F)c3)oc2c1

Procedure:
The title compound was prepared in substantially the same manner as described in Example 1, from 2,4-dimethoxyaniline, and 3-fluoro-4-methoxybenzoic acid and was obtained as a white solid, m.p. 269-271° C.; MS m/e 244 (M−H)+.
Reaction SMILES: NC1C=CC(C[N:9]2[C:19](=[O:20])[C:18]3[N:21]4[C:11](=[CH:12][N:13]=[C:14]4[CH:15]=[CH:16][CH:17]=3)[C:10]2=[O:22])=CC=1.C(N(CC)CC)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl>[N:13]1[CH:12]=[C:11]2[N:21]3[C:18](=[CH:17][CH:16]=[CH:15][C:14]=13)[C:19](=[O:20])[NH:9][C:10]2=[O:22]
Reactant: Nc1ccc(Cn2c(=O)c3cccc4ncc(c2=O)n43)cc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=c1[nH]c(=O)c2cnc3cccc1n32

Procedure:
To a suspension of 1.46 g (5.0 mmol) of 4-[4-(amino)phenylmethyl]-4,5-dihydro-3H-1,4,8b-triazaacenaphthylene-3,5-dione and 1.05 ml (7.5 mmol) of triethylamine in methylene chloride (100 ml) was added dropwise, while stirring under ice-cooling, 1.01 ml (6.0 mmol) of trifluoromethanesulfonic acid anhydride. The mixture was stirred for one hour at room temperature. The reaction mixture was washed with 1N-HCl, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was eluted by column chromatography (eluent:chloroform/ethyl acetate=1:1) to afford 502 mg of 4,5-dihydro-4-[4-bis(trifluoromethane sulfonyl)imido)phenylmethyl]-3H-1,4,8b-triazaacenaphthylene-3,5-dione (18.1%, a pale reddish brown solid).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[OH:10])[CH:5]=[O:6].[OH-].[K+].I[CH2:15][CH3:16]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[O:10][CH2:15][CH3:16])[CH:5]=[O:6]
Reactant: CCI
Reactant: O=Cc1cc(F)c(O)c(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCOc1c(F)cc(C=O)cc1Cl
Yield: 98 %

Procedure:
3-Chloro-5-fluoro-4-hydroxybenzaldehyde (1.0 gram, 5.7 mmol) in THF (40 mL) was heated at reflux for 17 hours with KOH (534 mg, 9.5 mmol, 1.7 eq) in water (5 mL) and iodoethane (1 mL, 2.2 eq). The reaction was then transferred to a separatory funnel with water and extracted with methylene chloride (thrice, 150 mL each). The combined organic layers were washed with 10% aqueous HCl (40 mL), dried (MgSO4), and concentrated to a viscous orange liquid to yield 1.13 g of 3-chloro-4-ethoxy-5-fluorobenzaldehyde (98%). 1H-NMR (500 MHz, CDCl3): 9.84 (d, J=1.9 Hz, 1H), 7.71 (t, J=1.6 Hz, 1H), 7.53 (dd, J=1.9, 10.7 Hz, 1H), 4.37-4.32 (m, 2H), 1.47-1.40 (m, 3H).