Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]([CH2:57][CH2:58][O:59][CH3:60])[CH2:9][CH2:10][N:11]([C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[C:21](=[O:25])[N:20]([CH2:26][C:27]([O:29][C@H:30]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH:48]([F:50])[F:49])=[C:43]([O:51][CH2:52][CH:53]3[CH2:55][CH2:54]3)[CH:42]=1)[CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][N+:35]([O-:39])=[CH:34][C:33]=1[Cl:40])=[O:28])[C:19]2=[O:56])[S:12]([CH3:15])(=[O:14])=[O:13])=O)(C)(C)C>C(Cl)Cl.Cl.O1CCOCC1>[Cl:40][C:33]1[CH:34]=[N+:35]([O-:39])[CH:36]=[C:37]([Cl:38])[C:32]=1[CH2:31][C@@H:30]([C:41]1[CH:46]=[CH:45][C:44]([O:47][CH:48]([F:49])[F:50])=[C:43]([O:51][CH2:52][CH:53]2[CH2:54][CH2:55]2)[CH:42]=1)[O:29][C:27](=[O:28])[CH2:26][N:20]1[C:19](=[O:56])[C:18]2[C:22](=[CH:23][CH:24]=[C:16]([N:11]([CH2:10][CH2:9][NH:8][CH2:57][CH2:58][O:59][CH3:60])[S:12]([CH3:15])(=[O:13])=[O:14])[CH:17]=2)[C:21]1=[O:25]
Reactant: COCCN(CCN(c1ccc2c(c1)C(=O)N(CC(=O)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC3CC3)c1)C2=O)S(C)(=O)=O)C(=O)OC(C)(C)C
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: COCCNCCN(c1ccc2c(c1)C(=O)N(CC(=O)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC3CC3)c1)C2=O)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 79 %

Procedure:
To a solution of (S)-4-(2-(2-(5-(N-(2-(tert-butoxycarbonyl(2-methoxyethyl)amino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.078 g, 0.086 mmol) in dry DCM (3 ml), 4M HCl in dioxane (0.103 ml, 0.412 mmol) was added, and the mixture was stirred for at room temperature overnight. Additional 4M HCl in dioxane (0.086 ml, 0.344 ml) was added, and the reaction was stirred at the same temperature for 72 hours. The mixture was washed with aqueous sat. NaHCO3; the organic phase was dried over sodium sulfate and the solvent was removed affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-(2-methoxyethylamino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide as a yellow solid (54.72 mg, 0.068 mmol, 79% yield, MS/ESI+ 801.13 [MH]+, [αD]=−20.82, c=0.512, MeOH). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.43 (s, 2H), 7.98 (s, 1H), 7.96 (dd, 1H), 7.90 (dd, 1H), 7.19 (d, 1H), 7.09 (d, 1H), 6.97 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.43 (s, 2H), 3.91-4.02 (m, 2H), 3.86 (t, 2H), 3.39 (dd, 1H), 3.30 (t, 2H), 3.23 (dd, 1H), 3.19 (s, 3H), 3.13 (s, 3H), 2.56-2.67 (m, 4H), 1.05-1.38 (m, 1H), 0.48-0.69 (m, 2H), 0.27-0.48 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1)[N:8]=[CH:7][C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:5]2[OH:22].C(=O)([O-])[O-].[K+].[K+].[CH:29]1([CH2:32]Br)[CH2:31][CH2:30]1>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1)[N:8]([CH2:32][CH:29]1[CH2:31][CH2:30]1)[CH:7]=[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:5]2=[O:22]
Reactant: BrCC1CC1
Reactant: CCOC(=O)c1cnc2cc(-n3cccc3)c(F)cc2c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(CC2CC2)c2cc(-n3cccc3)c(F)cc2c1=O
Temperature: 80 °C
Reaction time: 12 h
Yield: 62.3 %

Procedure:
A mixture of 3.6 g (0.012 mol) of ethyl 6-fluoro-7-(pyrrol-1-yl)-4-hydroxyquinoline-3-carboxylate and 4.15 g (0.03 mol) of potassium carbonate in 30 ml of dimethlformamide is heated for 30 minutes at 80° C. and left to cool, 8 g (0.06 mol) of cyclopropylmethyl bromide are added, the mixture is kept for 12 hours at 90° C. and left to cool, 80 ml of a water/ice mixture are added and the precipitate formed is filtered off, washed with water and recrystallized from ethanol to give 2.65 g of a solid melting at 125°-127° C.
Reaction SMILES: [CH3:1][C:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11](Cl)=[CH:12][CH:13]=1)=[O:7].[N:17]1([C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:34])([F:33])[F:32])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>>[CH3:1][C:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:9]=[N:10][C:11]([N:20]2[CH2:21][CH2:22][N:17]([C:23](=[O:24])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]([F:34])([F:32])[F:33])[CH2:18][CH2:19]2)=[CH:12][CH:13]=1)=[O:7]
Reactant: O=C(c1ccccc1C(F)(F)F)N1CCNCC1
Reactant: CC(C)(C)CCNC(=O)c1ccc(Cl)nn1
Product: CC(C)(C)CCNC(=O)c1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 15, making variations only as required to use 6-chloropyridazine-3-carboxylic acid (3,3-dimethylbutyl)amide in place of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide to react with piperazin-1-yl-(2-trifluoromethylphenyl)methanone, the title compound was obtained as a white solid (17% yield). 1H NMR (400 MHz, CDCl3) δ 8.05, 7.83-7.72, 7.64, 7.57, 7.38, 6.98, 4.09-3.66, 3.50-3.45, 3.37-3.34, 1.57-1.52, 0.96. MS (ES+) m/z 464.6 (M+1).
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:8][CH:9]=1.[C:14]1(=[O:18])[O:17][CH2:16][CH2:15]1.Cl>O.CN(C)C=O>[F:13][C:10]([F:11])([F:12])[C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[O:3][CH2:16][CH2:15][C:14]([OH:18])=[O:17]
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: O=C1CCO1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)CCOc1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium hydride (550 mg) was added to an N,N-dimethylformamide (20.0 mL) solution of 3-hydroxybenzotrifluoride (2.0 g), and the reaction mixture was stirred at room temperature for one hour. β-Propiolactone (1.0 mL) was added thereto, and the solution was stirred at room temperature for 2.5 hours. Water was then added to the solution, and the pH was adjusted to 2 with 2 N hydrochloric acid. The solution was extracted with ethyl acetate. The organic layer was sequentially washed with water and a saturated brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and n-hexane was then added to the residue to perform crystallization. The title compound (2.2 g) was obtained as colorless crystals.
Reaction SMILES: [K].[O:2]=[CH:3][C@@H:4]([C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9])[OH:7])[OH:5].[Os:14].C(O)(=[O:17])C>>[O:2]=[CH:3][C@@H:4]([C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9])[OH:7])[OH:5].[O:2]=[C:3]([O-:17])[C@@H:4]([C@H:6]([C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9])[OH:7])[OH:5].[Os:14]
Reactant: CC(=O)O
Agent: [Os]
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: [K]
Product: O=C([O-])[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
Potassium tricetato dioxo osmate(VI) reacts with glucose in glacial acetic acid to yield a brown or black product, depending upon the quantity of carbohydrate available for reaction and the reaction conditions employed. In situations in which there are two equivalents of glucose per equivalent of osmium, the product is black and contains 20 to 50% osmium. Larger quantities of glucose, or excess gluconate, results in a brown product with 10 to 20% osmium. Mild re-fluxing conditions (e.g. steam bath) favors the formation of the brown product.
Reaction SMILES: [NH2:1][C:2]1[S:20][C:5]2[CH2:6][N:7](C(OCC3C=CC=CC=3)=O)[CH2:8][CH2:9][C:4]=2[C:3]=1[C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Br.CCCCCC>C(O)(=O)C.O>[NH2:1][C:2]1[S:20][C:5]2[CH2:6][NH:7][CH2:8][CH2:9][C:4]=2[C:3]=1[C:21](=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: Nc1sc2c(c1C(=O)c1ccccc1)CCN(C(=O)OCc1ccccc1)C2
Agent: Br
Solvent: CCCCCC
Solvent: O
Solvent: CC(=O)O
Product: Nc1sc2c(c1C(=O)c1ccccc1)CCNC2
Yield: 92 %

Procedure:
To a cooled and stirred suspension of protected 2-amino-3-benzoyl-6-benzyloxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (0.01 mol) in acetic acid (2 mL), as prepared in Example 7, was added a solution of HBr (33%) in acetic acid (10 mL). After stirring at room temperature for 4 h (TLC control), n-hexane was added and the resulting suspension was evaporated under vacuum to give a solid which was dissolved in water (10 mL) and neutralized with NAOH (5% solution). The precipitated solid was chromatographed on a silica gel column eluting with an ethyl acetate and petroleum ether mixture to give 2-amino-3-benzoyl4,5,6,7-tetrahydrothieno[2,3-c]pyridine.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[P:11]([O:19][CH:20]([O:23][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:21]I)([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])=[O:12].CCOCC.C(Cl)Cl>C1(C)C=CC=CC=1.CCOCC>[P:11]([O:19][C:20]([O:23][C:24](=[O:31])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[CH2:21])([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])=[O:12]
Reactant: CCOP(=O)(OCC)OC(CI)OC(=O)c1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOCC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: C=C(OC(=O)c1ccccc1)OP(=O)(OCC)OCC
Reaction time: 0.5 h
Yield: 44.8 %

Procedure:
Lithium bis(trimethylsilyl)amide (1.0M solution in hexanes, 1.752 ml, 1.752 mmol) was added dropwise to a solution of the iodobenzoate XIX (0.250 g, 0.584 mmol) in toluene (50 ml) at -78° C. and allowed to stir for 30 min. The reaction mixture was then diluted with Et2O (150 ml), washed with saturated aqueous NaHSO4 (3×25 ml), 10% aqueous sodium phosphate buffer (pH=7) (1×25 ml), dried (MgSO4), and concentrated in vacuo. Flash chromatography (5% Et2O/CH2Cl2) afforded the geminal benzoate XX (78.6 mg, 44.8% yield) as a clear, colorless oil: 1H NMR (CDCl3, 400 MHz) d 8.10 (d, 2 H, J=7.5 Hz, C7 - and C8 -H), 7.63 (t, 1 H, J=7.5 Hz, C9 - and C8 -H, C9 - and C7 -H), 7.48 (t, 2 H, J=7.5 Hz, C8 - and C7 -H, C8 - and C9 -H), 4.78 (dd, 1 H, J=3.5 Hz, C2b - and C2a -H; J=2.2 Hz, C2b -H and P), 4.54 (dd, 1 H, J=3.5 Hz, C2a - and C2b -H; J=1.1 Hz, C2a -H and P), 4.23 (m, 4 H), 1.34 (dt, 6 H, J=7.0 Hz, C4- and C3 -H; J=1.1 Hz, C4 -H and P); 13C NMR (CDCl3, 100 MHz) d 164.0, 149.3 (d, J=5 Hz), 134.9, 131.1, 129.4, 128.9, 86.1 (d, J=3 Hz), 65.4 (d, J=6 Hz), 16.1 (d, J=7 Hz); 31P NMR (H3PO4, 146 MHz) d -7.19; IR (NaCl solution cell, CDCl3) 2988, 2932, 1752, 1672, 1277, 1204, 1177, 1063, 1034, 999, 916, 706; LRMS, m/e (relative intensity) 301.1 (15.8), 259.0 (55.9), 155.0 (6.7), 106.0 (22.1), 105.0 (100.0), 81.0 (7.3), 77.0 (37.7), 51.0 (10.3); HRMS for C13H17O6P [M+H+ ], calcd. 301.0763; found, 301.0843.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].[Cl:31][C:32]1[CH:33]=[N:34][CH:35]=[C:36]([Sn](CCCC)(CCCC)CCCC)[CH:37]=1.CCOC(C)=O.Cl>CN(C=O)C.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([C:36]3[CH:35]=[N:34][CH:33]=[C:32]([Cl:31])[CH:37]=3)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cncc(Cl)c1
Reactant: COC(=O)c1nc(Br)c2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1nc(-c2cncc(Cl)c2)c2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Temperature: 120 °C
Yield: 44.9 %

Procedure:
A mixture of 1-benzyl-8-bromo-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (80 mg, 0.17 mmol), 3-chloro-5-tributylstannanyl-pyridine (104 mg, 0.26 mmol) and PdCl2(PPh3)2 (24 mg, 0.034 mmol) in 4 mL of DMF was heated at 120° C. for 3 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and brine were added. 1 M HCl was added with stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was chromatographed (0-15% EtOAc/CH2Cl2) to give 38 mg of the title compound. MS: (+) m/z 498.29 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][CH2:22][N:23]1[C:27](=[O:28])[C:26]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]2[C:24]1=[O:33]>CN(C)C=O>[C:24]1(=[O:33])[N:23]([CH2:22][CH2:21][CH2:20][O:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]3)[C:27](=[O:28])[C:26]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]12
Reactant: O=c1ccc2cc(O)ccc2[nH]1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCOc1ccc2[nH]c(=O)ccc2c1
Temperature: 75 °C
Reaction time: 1 h
Yield: 63.4 %

Procedure:
A suspension of 6-hydroxycarbostyril (300 g) and potassium carbonate (308 g) in dimethylformamide (2 liters) is heated with stirring at 70-80° C. for one hour. To the suspension is added N-(3-bromopropyl)phthalimide (498 g), and the mixture is further stirred at the same temperature for 9 hours. The reaction solution is poured into ice-water, and the precipitated crystals are collected by filtration, washed successively with water, ethanol and diethyl ether, and dried to give 6-(3-phthalimidopropoxy)carbostyril (410 g) as a white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.Cl.[NH2:11][OH:12].CCO.CCN(C(C)C)C(C)C>C(OCC)(=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6](=[N:11][OH:12])[NH2:7])=[CH:4][CH:3]=1
Reactant: N#Cc1ccc(Cl)cc1
Reactant: NO
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: NC(=NO)c1ccc(Cl)cc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 64.7 %

Procedure:
In a 100 mL round-bottomed flask, 4-chlorobenzonitrile (2 g, 14.5 mmol) and hydroxylamine hydrochloride (1.00 g, 14.5 mmol) were combined with EtOH (20 ml) to give a colorless solution. DIEA (2.82 g, 3.81 ml, 21.8 mmol) was added and the reaction mixture was heated at 100° C. and stirred for 6 h. The crude reaction mixture was diluted with ethyl acetate (100 ml) and filtered. The solid was collected, washed with ethyl acetate and dried to afford 1.6 g (64%) of 4-chloro-N′-hydroxybenzimidamide as a white solid.
Reaction SMILES: [Cl:1][CH:2]([Cl:6])[C:3](Cl)=[O:4].[NH2:7][C:8]1[CH:21]=[CH:20][CH:19]=[CH:18][C:9]=1[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11]>ClCCl.C(N(CC)CC)C>[C:10]([C:9]1[CH:18]=[CH:19][CH:20]=[CH:21][C:8]=1[NH:7][C:3](=[O:4])[CH:2]([Cl:6])[Cl:1])(=[O:11])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Nc1ccccc1C(=O)c1ccccc1
Reactant: O=C(Cl)C(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccccc1)c1ccccc1NC(=O)C(Cl)Cl
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Dichloroacetylchloride (88 ml) in dichloromethane (200 ml) was added dropwise to a stirred solution of 2-aminobenzophenone (157.6g) in dichloromethane (400 ml) and triethylamine (116 ml) while keeping the temperature between 20°-30°C by cooling in ice. On completion of the addition the reaction was stirred at room temperature for 1.5 hours. The reaction mixture was washed with successive portions of distilled water-dilute hydrochloric acid and finally distilled water. After drying over anhydrous magnesium sulphate the solvent was removed under reduced pressure to leave a solid which on recrystallisation from absolute, ethanol gave 222 g of 2'-benzoyl-2,2-dichloroacetanilide, m.p. 112°-114°C.
Reaction SMILES: CO[C:3]([C:5]1[CH:12]=[CH:11][CH:10]=[C:8](C)[C:6]=1O)=[O:4].C1C(=NNC2C=CC(/C=C/C3C=CC(NN=C4C=CC(=O)C=C4)=CC=3S([O-])(=O)=O)=C(S([O-])(=O)=O)C=2)C=C[C:15](=[O:16])C=1.[Na+].[Na+]>O>[OH:16][CH2:15][CH:10]1[CH2:8][CH2:6][CH:5]([CH2:3][OH:4])[CH2:12][CH2:11]1
Reactant: O=C1C=CC(=NNc2ccc(/C=C/c3ccc(NN=C4C=CC(=O)C=C4)cc3S(=O)(=O)[O-])c(S(=O)(=O)[O-])c2)C=C1
Reactant: COC(=O)c1cccc(C)c1O
Agent: *CC*
Agent: O=C(O)c1ccc(C(=O)O)cc1
Agent: [Na+]
Solvent: O
Product: OCC1CCC(CO)CC1

Procedure:
100 g of polyethylene terephthalate fibres in 4 l of water are dyed with 1 g of the dyestuff prepared according to the above example, which has first been brought to a finely divided state in the presence of dispersing agents, the dyeing being carried out in the presence of 15 g of o-cresotic acid methyl ester as the carrier for 2 hours at 100°C and pH 4.5. A brilliant yellow-tinged pink dyeing is obtained, which is distinguished by good built-up and high fastness to washing, thermofixing, rubbing and light. A similar colouration is obtained if polyester fibres from 1,4-bis-(hydroxymethyl)-cyclohexane and therephthalic acid are used.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[C:12]([O:22][CH3:23])[CH:11]=2)[N:3]=1.[O-:24][CH2:25][CH3:26].[Na+]>C(O)C>[CH2:25]([O:24][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH:20]=[C:19]([CH3:21])[N:18]=[CH:17]3)=[C:12]([O:22][CH3:23])[CH:11]=2)[N:3]=1)[CH3:26]
Reactant: CC[O-]
Reactant: COc1cc(Nc2nc(C)cc(Cl)n2)ccc1-n1cnc(C)c1
Agent: [Na+]
Solvent: CCO
Product: CCOc1cc(C)nc(Nc2ccc(-n3cnc(C)c3)c(OC)c2)n1
Reaction time: 0.5 h
Yield: 81.9 %

Procedure:
A mixture of (4-chloro-6-methyl-pyrimidin-2-yl)-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine (165 mg, 0.5 mmol) and sodium ethoxide (54 mg, 0.75 mmol) in ethanol (3 ml) was heated for 30 min to 160° C. in a microwave oven. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was stirred with diethyl ether for 30 min to yield the title compound as a brown solid (139 mg, 82%).
Reaction SMILES: [CH:1](I)([CH3:3])[CH3:2].[CH2:5]([O:12][C:13]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][C:14]=1[C:15]([NH:17][C:18]1[CH:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=[CH:24][C:19]=1[C:20]([O:22][CH3:23])=[O:21])=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+]>C(=O)([O-])[O-].[K+].[K+].C(#N)C>[CH2:5]([O:12][C:13]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:39][CH2:40][N:41]([CH:1]([CH3:3])[CH3:2])[CH2:42][CH2:43]2)=[CH:34][C:14]=1[C:15]([NH:17][C:18]1[CH:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=[CH:24][C:19]=1[C:20]([O:22][CH3:23])=[O:21])=[O:16])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: CC(C)I
Reactant: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCNCC2)ccc1OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCN(C(C)C)CC2)ccc1OCc1ccccc1
Temperature: 25 °C

Procedure:
Potassium carbonate (0.033 mg) and isopropyl iodide (0.024 mL) were sequentially added to an acetonitrile (1.9 mL) suspension of methyl 2-(2-(benzyloxy)-5-(piperidin-4-yl)benzamido)-4-phenylbenzoate (0.13 g), followed by heating to reflux for 1 hour. The reaction mixture was cooled to room temperature, and potassium carbonate (6.7 mg) and isopropyl iodide (4.8 μL) were sequentially added thereto, followed by heating to reflux for 2 hours. After cooling the reaction mixture to room temperature, the solvent was evaporated under reduced pressure, and ethyl acetate and a saturated aqueous solution of sodium bicarbonate were added to the residue. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-95% chloroform/methanol] to obtain 0.12 g of methyl 2-(2-(benzyloxy)-5-(1-isopropylpiperidin-4-yl)benzamido)-4-phenylbenzoate as an orange oily sub stance.
Reaction SMILES: I[CH2:2][O:3][C:4]([O:6][CH2:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])=[O:5].[Na].[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[CH2:27][NH:28][C:29]([C:31]1[C:32](=[O:47])[C:33]([OH:46])=[C:34]2[C:39](=[O:40])[N:38]3[C@@H:41]([CH3:44])[CH2:42][O:43][C@@H:37]3[CH2:36][N:35]2[CH:45]=1)=[O:30].C(=O)([O-])[O-].[K+].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[CH2:27][NH:28][C:29]([C:31]1[C:32](=[O:47])[C:33]([O:46][CH2:2][O:3][C:4]([O:6][CH2:7][C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[O:5])=[C:34]2[C:39](=[O:40])[N:38]3[C@@H:41]([CH3:44])[CH2:42][O:43][C@@H:37]3[CH2:36][N:35]2[CH:45]=1)=[O:30]
Reactant: C[C@H]1CO[C@@H]2Cn3cc(C(=O)NCc4ccc(F)cc4F)c(=O)c(O)c3C(=O)N12
Reactant: O=C(COC(=O)OCI)OCc1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])O
Product: C[C@H]1CO[C@@H]2Cn3cc(C(=O)NCc4ccc(F)cc4F)c(=O)c(OCOC(=O)OCC(=O)OCc4ccccc4)c3C(=O)N12

Procedure:
The title compound was prepared from phenylmethyl ({[(iodomethyl)oxy]carbonyl}oxy)acetate (819 mg, 2.34 mmol), 1b (500 mg, 1.17 mmol), potassium carbonate (485 mg, 3.51 mmol), and tetrabutylammonium hydrogen sulfate (397 mg, 1.17 mmol), using a similar process to that described in example 1. 1H NMR (CDCl3) δ 10.18 (m, 1H), 8.36 (s, 1H), 7.34-7.27 (m, 6H), 6.76 (m, 2H), 5.98 (d, J=6.8 Hz, 1H), 5.85 (d, J=6.4 Hz, 1H), 5.27 (dd, J=10, 4 Hz, 1H), 5.15 (s, 2H), 4.66 (s, 2H), 4.60 (m, 2H), 4.39-4.23 (m, 3H), 3.88 (m, 1H), 3.64 (m, 1H), 1.35 (d, J=6.4 Hz, 3H). ES+ MS: 628 (M+1).
Reaction SMILES: [O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:6]=2[NH:5][CH2:4][CH:3]1[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].Br[CH:23]1[CH2:28][CH2:27][CH2:26][CH:25]=[CH:24]1.C(=O)(O)[O-].[Na+]>CO>[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:6]=2[N:5]([CH:28]2[CH2:27][CH2:26][CH2:25][CH:24]=[CH:23]2)[CH2:4][CH:3]1[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]
Reactant: Cc1ccc2c(c1)NC(=O)C(NC(=O)OC(C)(C)C)CN2
Reactant: BrC1C=CCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: Cc1ccc2c(c1)NC(=O)C(NC(=O)OC(C)(C)C)CN2C1C=CCCC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 35.6 %

Procedure:
2-Oxo-3-tert-butoxycarbonylamino-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (3.00 g) obtained from Referential Example 7 was suspended in methanol (30 ml), 90% 3-bromocyclohexene (6.08 g) and sodium bicarbonate (2.85 g) were added, and the mixture was stirred for 5 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water (100 ml) was added to the residue, extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby obtain 1.36 g of the titled compound.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].C(N(CC)CC)C.Cl[CH2:18][CH2:19][CH2:20][C:21](Cl)=[O:22].CC(C)([O-])C.[K+].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:18][CH2:19][CH2:20][C:21]2=[O:22])=[CH:4][C:3]=1[CH3:9]
Reactant: Cc1cc(N)ccc1Br
Reactant: O=C(Cl)CCCCl
Agent: CC(C)(C)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1cc(N2CCCC2=O)ccc1Br
Temperature: 2.5 °C
Reaction time: 1 h
Yield: 89.8 %

Procedure:
A stirred solution of 4-bromo-3-methylaniline (50.3 g, 0.27 mole) and triethylamine (41.4 ml, 0.30 mole) in THF (250 ml) at 0° C. under argon was treated dropwise with 4-chlorobutyryl chloride (33.4 ml, 0.30 mole). The mixture was stirred for 1 hour at 0-5° C., then potassium t-butoxide (82.5 g, 0.74 mole) was added portionwise over 20 minutes, maintaining temperature below 25° C. The reaction mixture was stirred at 25° C. for a further 2.5 hrs, then treated with water (100 ml), followed after 0.25 hrs with 10% Na2CO3 solution and then extracted with ethyl acetate. The extract was washed with water, dil. HCl acid, then brine, dried (Na2SO4) and concentrated in vacuo to afford the title compound as a pale yellow solid (61.6 g, 89%).