Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:4][N:5]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12][N:11]([CH2:17][C:18]([OH:20])=[O:19])[CH2:10][CH2:9][N:8]([CH2:21][C:22]([OH:24])=[O:23])[CH2:7][CH2:6]1)([OH:3])=[O:2].[OH-].C([N+](C)(C)C)C1C=CC=CC=1.Cl[CH2:38][C:39]([NH2:41])=[O:40].Cl>O>[C:1]([CH2:4][N:5]1[CH2:16][CH2:15][N:14]([CH2:38][C:39](=[O:40])[NH2:41])[CH2:13][CH2:12][N:11]([CH2:17][C:18]([OH:20])=[O:19])[CH2:10][CH2:9][N:8]([CH2:21][C:22]([OH:24])=[O:23])[CH2:7][CH2:6]1)([OH:3])=[O:2]
Reactant: NC(=O)CCl
Reactant: O=C(O)CN1CCNCCN(CC(=O)O)CCN(CC(=O)O)CC1
Agent: C[N+](C)(C)Cc1ccccc1
Agent: Cl
Agent: [OH-]
Solvent: O
Product: NC(=O)CN1CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC1
Temperature: 80 °C
Yield: 94.4 %

Procedure:
The pH of a solution of 1.40 g of 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane in about 4 ml water was adjusted to 9.5 using 40% aqueous benzyltrimethylammonium hydroxide. To the resulting solution was added 412 mg a-chloroacetamide. The temperature was increased to 80° C. and base was added as necessary to maintain the pH at 9.5-10. After 3 hours the solution was cooled to room temperature and acidified to pH 3 with concentrated HCl. The resulting solution was evaporated under reduced pressure to a colorless sludge. The mixture was taken up in about 25 ml MeOH and re-evaporated. The thick residue was triturated with a 1:1 mixture of acetone and ethanol to provide a granular solid and colorless solution. The solid was collected by filtration, washed with acetone/ethanol followed by acetone and finally ether, then dried in a vacuum oven at 50° for 2 hours. Obtained was 1.54 g of the title compound as a colorless powder. The product was twice crystallized from ethanol/water.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(Cl)C2N=NN(CC3C=CC(OC)=CC=3)C=2N=1)(C)(C)C.N1CC[C@H](O)C1>>[C:1]([C:5]1[N:6]=[C:7]([N:23]2[CH2:28][CH2:27][C@H:25]([OH:26])[CH2:24]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[C:9]=2[N:10]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: COc1ccc(Cn2nnc3c(N4CCOCC4)nc(C(C)(C)C)nc32)cc1
Agent: COc1ccc(Cn2nnc3c(Cl)nc(C(C)(C)C)nc32)cc1
Agent: O[C@H]1CCNC1
Product: COc1ccc(Cn2nnc3c(N4CC[C@H](O)C4)nc(C(C)(C)C)nc32)cc1

Procedure:
In analogy to the procedure described for the synthesis of 4-(5-tert-butyl-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)morpholine (example 58, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(4-methoxybenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (S)-pyrrolidin-3-ol and isolated as light-yellow solid. MS (m/e): 383.3 (MH+).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[OH-].[Na+]>FC(F)(F)C(O)=O.CCOCC.[Pt]=O>[NH:1]1[CH:9]2[CH:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][CH:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)c1cc2ccccc2[nH]1
Agent: O=[Pt]
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CCOCC
Product: CCOC(=O)C1CC2CCCCC2N1

Procedure:
Dissolve 27.0 g of ethyl indole-2-carboxylate in 250 ml of trifluoroacetic acid. Add 2.05 g of platinum oxide and hydrogenate the mixture at 50 lb/in2 at room temperature. Filter the mixture and concentrate the filtrate in vacuo to give a residue. Suspend the residue in ether and treat with cold dilute sodium hydroxide solution. Dry the organic layer over magnesium sulfate and concentrate it to give octahydro-1H-indole-2-carboxylic acid, ethyl ester, a pale yellow oil.
Reaction SMILES: C([O:8][C:9](=[O:42])[CH2:10][C@@H:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)=[CH:26]1)[C:12]([NH:14][C@@H:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])C1C=CC=CC=1>CCOC(C)=O.[Pd]>[CH2:18]([C@H:15]([NH:14][C:12](=[O:13])[C@H:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:31]=[CH:32][C:33]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[CH:34][CH:35]=2)=[CH:26]1)[CH2:10][C:9]([OH:42])=[O:8])[CH2:16][OH:17])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(C[C@H](C(=O)N[C@H](CO)Cc1ccccc1)n1ccc(-c2ccc(-c3ccccc3)cc2)c1)OCc1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C(O)C[C@H](C(=O)N[C@H](CO)Cc1ccccc1)n1ccc(-c2ccc(-c3ccccc3)cc2)c1
Reaction time: 20 h
Yield: 83.6 %

Procedure:
A suspension of 10% Pd/C (wet DeGussa type, 15 mg) and N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester (68 mg, 0.12 mmol) in EtOAc (5 mnL) was stirred under H2 for 20 hours. The catalyst was filtered onto Celite and rinsed with MeOH. The filtrate was concentrated under reduced pressure to give a yellow oil, which was purified via flash column chromatography with a 1% HOAc/2-5% MeOH/CH2Cl2 stepwise gradient elution to provide 47 mg (82%) of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid as a white solid. 1H NMR (CDCl3): δ 7.66-7.48 (m, 3H), 7.42 (t, 2H, J=7.2 Hz), 7.34-7.28 (m, 1H), 7.21-7.12 (m, 2H), 7.04-6.96 (m, 1H), 6.94 (bs, 1H), 6.68 (dd, 1H, J=2.5, 2.5 Hz), 6.55 (dd, 1H, J=1.6, 1.6 Hz), 5.78 (bd, 1H, J=7.5Hz), 4.90 (t, 1H, J=7.2 Hz), 4.36-4.02 (m, 1H), 3.68 (dd, 1H, J=3.4, 11.2 Hz), 3.50 (dd, 1H, J=5.3, 9.0 Hz), 3.31 (dd, J=5.9, 7.4 Hz), 3.12 (dd, 1H, J=7.2, 17.1 Hz), 2.74 (ddd, 1H, J=6.2, 14.3 14.3 Hz), 2.68 (ddd, J=8.7, 14.0, 14.3 Hz). IR (film): 3387, 3028, 2931, 1715, 1660, 1532, 1494, 1204, 702, 698 cm-1. HRFABMS: Calculated for C29H28N2O4Cs (M+Cs+): 643.1209. Found: 643.1185. Anal. calculated for C29H28N2O4.0.1 CHCl3.0.35 H2O: C, 71.80; H, 5.96; N, 5.75. Found: C, 71.92; H, 5.87; N, 5.77.
Reaction SMILES: [CH3:1][I:2].[CH3:3][N:4]1[CH2:9][CH2:8][CH2:7][CH:6]([C:10]2[O:14][N:13]=[C:12]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][C:16]=3[CH3:24])[N:11]=2)[CH2:5]1>CC(C)=O>[I-:2].[CH3:3][N+:4]1([CH3:1])[CH2:9][CH2:8][CH2:7][CH:6]([C:10]2[O:14][N:13]=[C:12]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][C:16]=3[CH3:24])[N:11]=2)[CH2:5]1
Reactant: CI
Reactant: Cc1[nH]c2ccccc2c1-c1noc(C2CCCN(C)C2)n1
Solvent: CC(C)=O
Product: Cc1[nH]c2ccccc2c1-c1noc(C2CCC[N+](C)(C)C2)n1
Product: [I-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 67.6 %

Procedure:
Methyl iodide (200mg) was added to a stirred solution of 1-methyl-3-[3-(methylindol-3-yl)-1,2,4-oxadiazol-5-yl]piperidine (300 mg) in anhydrous acetone (20 ml) at room temperature. After stirring at room temperature for two hours the precipitate was isolated by filtration and dried to afford the title compound (300 mg), mp 250° C.; Found C, 49.09; H, 5.34; N, 12.43, C18H23N4OI requires C, 49.32; H, 5.29; N, 12.78%; δH (360 MHz, DMSO), 1.68-2.18 (4 H, m, 2×CH2), 3.21 (3 H, s, NMe), 3.24 (3 H, s, NMe), 3.40-4.06 (5 H, m, 2×CH2, CH), 3.94 (3 H, s, NMe), 7.23-7.34 (2 H, m, H-5, H-6), 7.58 (1 H, d, J=7, H-7), 8.04 (1 H, d J=7, H-4), 8.10 (l H, s, H-2); M/Z 311(100), 185(30), 93(59).
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[Cl:5][C:6]1[C:12]([NH:13][S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])=[CH:11][C:9]([NH2:10])=[C:8]([F:19])[CH:7]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[Cl:5][C:6]1[C:12]([NH:13][S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])=[CH:11][C:9]([N:10]=[C:1]=[S:2])=[C:8]([F:19])[CH:7]=1
Reactant: CCS(=O)(=O)Nc1cc(N)c(F)cc1Cl
Reactant: S=C(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCS(=O)(=O)Nc1cc(N=C=S)c(F)cc1Cl
Yield: 49.3 %

Procedure:
Under a dry nitrogen atmosphere 0.84 ml (0.011 mole) of thiophosgene was added to a stirred solution of 2.8 g (0.011 mole) of 4-chloro-2-fluoro-5-(N-ethylsulfonylamino)aniline in 250 ml of chloroform. To this mixture was added dropwise 1.6 g (0.012 mole) of triethylamine. The resultant mixture was stirred at room temperature for approximately 18 hours. The solvent was removed from the mixture by evaporation under reduced pressure leaving an oily residue. This residue was purified by column chromatography on silica gel, eluting with methylene chloride/hexane (60/40) followed by methylene chloride, to yield 1.6 g of 4-chloro-5-(N-ethylsulfonylamino)-2-fluorophenyl isothiocyanate as a solid, m.p. 104°-105° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:5]2[Cl:19].[Li]CCCC.[CH3:25][C:26]1[S:27][C:28]([C:32](=[O:36])[CH:33]([CH3:35])[CH3:34])=[C:29]([CH3:31])[N:30]=1.C(=O)=O.CC(C)=O>C1COCC1>[Cl:12][C:7]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:5]([Cl:19])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:32]([C:28]3[S:27][C:26]([CH3:25])=[N:30][C:29]=3[CH3:31])([OH:36])[CH:33]([CH3:35])[CH3:34])[CH:3]=2)[N:8]=1
Reactant: Cc1nc(C)c(C(=O)C(C)C)s1
Reactant: Clc1nc2ccc(Br)cc2c(Cl)c1-c1ccccc1
Agent: O=C=O
Agent: [Li]CCCC
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: Cc1nc(C)c(C(O)(c2ccc3nc(Cl)c(-c4ccccc4)c(Cl)c3c2)C(C)C)s1
Temperature: -75 °C
Reaction time: 0.03 h

Procedure:
To a flask containing 6-bromo-2,4-dichloro-3-phenylquinoline (275 mg, 0.78 mmol, Intermediate 1: step c) was added THF (10 mL) to give a homogeneous clear solution. The solution was cooled in a dry ice—acetone bath and n-BuLi (2.5 M in hexanes, 0.28 mL, 0.7 mmol) was added which resulted in an immediate orange-brown homogeneous solution. After 2 minutes, a solution of 1-(2,4-dimethylthiazol-5-yl)-2-methylpropan-1-one (200 mg, 1.09 mmol, Intermediate 4: step b) in 3 mL THF was added. The reaction mixture was maintained at −75° C. for 5 minutes then the dry ice—acetone bath was replaced with a 0° C. ice-bath. After 20 minutes the ice-bath was removed and the mixture was stirred at room temperature for 20 minutes. The mixture was quenched after a total reaction time of 45 minutes with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (3×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (100% DCM increasing to 20% EtOAc/DCM) provided the title compound as a white amorphous solid. 1H NMR (500 MHz, CD2Cl2) δ 8.42 (d, J=1.9 Hz, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.81 (dd, J=8.9, 2.1 Hz, 1H), 7.57-7.46 (m, 3H), 7.41-7.27 (m, 2H), 2.77 (p, J=6.6 Hz, 1H), 2.52 (s, 3H), 2.19 (s, 3H), 1.16 (d, J=6.7 Hz, 3H), 0.81 (d, J=6.7 Hz, 3H); MS (ESI): mass calcd. for C24H22Cl2N2OS, 456.1, m/z found 457.0 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>CN(C1C=CN=CC=1)C>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([S:20]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)(=[O:22])=[O:21])=[CH:18][CH:19]=1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1cccc2cccnc12
Agent: CN(C)c1ccncc1
Product: COc1ccc(S(=O)(=O)Nc2cccc3cccnc23)cc1
Yield: 61.2 %

Procedure:
In the similar fashion using route 14 general procedure 27, 8-aminoquinoline (200 mg, 1.38 mmol), 4-methoxybenzenesulfonyl chloride (300 mg, 1.3 mmol) and DMAP (cat.) gave the title compound (250 mg, 58%) after purification by column chromatography with DCM/MeOH/NH3 (100-100:1:1 drop).
Reaction SMILES: C(O)(=O)C.[C:5]1(=[O:15])[O:10][C:8](=O)[C:7]2=[CH:11][CH:12]=[CH:13][CH:14]=[C:6]12.[F:16][C:17]([F:30])([F:29])[C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[NH2:21]>O.C1CCCCC1>[F:16][C:17]([F:29])([F:30])[C:18]1[CH:19]=[C:20]([N:21]2[C:5](=[O:15])[C:6]3=[CH:14][CH:13]=[CH:12][CH:11]=[C:7]3[C:8]2=[O:10])[CH:22]=[C:23]([C:25]([F:26])([F:28])[F:27])[CH:24]=1
Reactant: O=C1OC(=O)c2ccccc21
Reactant: Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCCCC1
Product: O=C1c2ccccc2C(=O)N1c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 55 °C

Procedure:
800 ml of glacial acetic acid are initially introduced into a three-necked flask provided with a thermometer, stirrer and water separator, and are warmed to 55° C. A mixture of 44.4 g (0.3 mol) of phthalic anhydride and 68.7 g (0.3 mol) of distilled 3,5-bis-trifluoromethylaniline is then added and the components are stirred vigorously. On warming to 108° C., a clear solution is obtained. This is kept under reflux at 117° C. for 21/2 hours and is then cooled. 100 ml of cyclohexane are added to the reaction mixture and the mixture is kept under reflux at 93° C. for 5 hours, during which the water of reaction can be removed in the water separator.
Reaction SMILES: [Na].[CH:2](OCC)=O.[CH:7]1([CH2:10][C:11]#[N:12])[CH2:9][CH2:8]1.[NH2:13][NH2:14]>CCOCC.C1COCC1.C(O)(=O)C>[CH:7]1([C:10]2[CH:2]=[N:14][NH:13][C:11]=2[NH2:12])[CH2:9][CH2:8]1
Reactant: NN
Reactant: N#CCC1CC1
Reactant: CCOC=O
Agent: [Na]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCOCC
Product: Nc1[nH]ncc1C1CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To 7 g (0.3 mol) of freshly cut sodium chunks in 220 mL dry ether under nitrogen and external ice cooling was added a solution of 25 mL (0.3 mol) ethyl formate followed by a solution of 25 g (0.3 mol) cyclopropylacetonitrile in 50 mL dry ether, and the mixture was stirred at room temperature for 2 days. 19 mL (0.3 mol) glacial acetic acid was added whilst maintaining the internal temperature at 10-12° C., the solids were filtered off and the filtrate was concentrated at below 20° C. The residue was treated with 300 mL (0.6 mol) 2 M hydrazine in THF, 5 mL glacial acetic acid and heated at reflux for 2 hours. After cooling, the mixture was concentrated and the desired product was obtained by kugelrohr distillation. The product was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[C:6]([CH3:10])[C:7]=1N=O.[O:12]1CCOCC1.CC(C)=O.[ClH:22]>O>[Cl:22][C:3]1[C:2]([CH3:1])=[C:7]([OH:12])[C:6]([CH3:10])=[CH:5][C:4]=1[OH:11]
Reactant: Cl
Reactant: C1COCCO1
Reactant: Cc1cc(O)cc(C)c1N=O
Solvent: CC(C)=O
Solvent: O
Product: Cc1cc(O)c(Cl)c(C)c1O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A mixture of 12.08 g of 3,5-dimethyl-4-nitrosophenol, 11.45 g of cuprous oxide, 100 ml of 1,4-dioxane, 10 ml of acetone and 100 ml of 6N hydrochloric acid was heated under reflux for 2 hours. The reaction mixture was poured into iced water, followed by extraction with ether. The extract was dried over anhydrous sodium sulfate and the solvent was then distilled off under reduced pressure. The residue was dissolved in 150 ml of dichloromethane. To the resulting solution, 3.61 g of sodium borohydride were added under ice cooling, followed by the dropwise addition of 50 ml of methanol at an internal temperature not higher than 10° C. The reaction mixture was stirred at room temperature for 90 minutes. The reaction mixture was concentrated by evaporation. The concentrate was poured into iced water. The resulting mixture was acidified with 3N hydrochloric acid. The precipitated product was collected by filtration, washed successively with water and n-hexane, whereby 5.93 g of the title compound were obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].F[C:16]1[CH:17]=[C:18]([CH:48]=[CH:49][CH:50]=1)[O:19][C:20]1[CH:21]=[C:22]([CH:45]=[CH:46][CH:47]=1)[O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40](F)[CH:39]=3)[CH:32]=2)[CH:25]=1.[NH2:51][C:52]1[CH:53]=[C:54]([CH:133]=[CH:134][CH:135]=1)[O:55]C1C=C(C=CC=1)OC1C=C(C2C(OC3C=CC=C(OC4C=CC=C(F)C=4)C=3)=CC=CC=2OC2C=CC=C(OC3C=CC=C(OC4C=CC=C(F)C=4)C=3)C=2C2C=CC=C(OC3C=CC=C(OC4C=CC=C(N)C=4)C=3)C=2)C=CC=1>CN1C(=O)N(C)CC1>[NH2:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][C:16]1[CH:17]=[C:18]([CH:48]=[CH:49][CH:50]=1)[O:19][C:20]1[CH:21]=[C:22]([CH:45]=[CH:46][CH:47]=1)[O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([O:55][C:54]4[CH:133]=[CH:134][CH:135]=[C:52]([NH2:51])[CH:53]=4)[CH:39]=3)[CH:32]=2)[CH:25]=1
Reactant: Nc1cccc(O)c1
Reactant: Nc1cccc(Oc2cccc(Oc3cccc(-c4c(Oc5cccc(Oc6cccc(F)c6)c5)cccc4Oc4cccc(Oc5cccc(Oc6cccc(F)c6)c5)c4-c4cccc(Oc5cccc(Oc6cccc(N)c6)c5)c4)c3)c2)c1
Reactant: Fc1cccc(Oc2cccc(Oc3cccc(Oc4cccc(Oc5cccc(F)c5)c4)c3)c2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCN(C)C1=O
Product: Nc1cccc(Oc2cccc(Oc3cccc(Oc4cccc(Oc5cccc(Oc6cccc(Oc7cccc(N)c7)c6)c5)c4)c3)c2)c1
Temperature: 210 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
In a nitrogen atmosphere, 1 g (9 mmole) of m-aminophenol was dissolved in 20 ml of DMI, and 2 g (15 mmole) of potassium carbonate was added, followed by stirring for 30 minutes. Then, 1 g (2 mmole) of 1,3-bis(3-(3-fluorophenoxy)phenoxy)benzene was added, and the mixture was stirred for 14 hours under heating at 210° C. The progress of the reaction was confirmed by HPLC. When the intermediate product, 3-(3-(3-aminophenoxy)phenoxy)phenyl-3-(3-(3-fluorophenoxy)phenoxy)phenyl ether almost disappeared, the reaction was terminated. Then, liquid separation was carried out in the same manner as in Example 2 to obtain an organic phase, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography to obtain 1.1 g (1.6 mmole, yield: 86%, purity (HPLC): 98%) of 1,3-bis(3-(3-(3-aminophenoxy)phenoxy)phenoxy)benzene as a yellow oily product. The structure and the properties of the compound are as follows.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7](=[O:9])[CH3:8])[N:6]=1.[Br:10]Br>Br>[BrH:10].[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([C:7](=[O:9])[CH2:8][Br:10])[N:6]=1
Reactant: CC(=O)c1c[nH]c(C)n1
Reactant: BrBr
Agent: Br
Product: Cc1nc(C(=O)CBr)c[nH]1
Yield: 93.9 %

Procedure:
2.40 g (19.3 mmol) of 1-(2-methyl-4-imidazolyl) ethanone was dissolved in 30 ml of 48% hydrogen bromide. To the stirred solution at 25° was added over a 5 minute period 3.36 g (21 mmol) of bromine dissolved in 5 ml 48% hydrogen bromide. The reaction was heated to 70° for 2.5 hours and then concentrated in vacuo to a dark oil. A mixture of isopropyl alcohol/ether was added and trituration of the oil gave a solid. This was collected by filtration and washed with ether to give 2.8 g (51%) of 1-(2-methyl-4-imidazolyl)-2-bromoethanone hydrobromide, mp 181° (dec.); nmr (DMSO-d6) (δ): 8.71 (s, 1H); 4.77 (s, 2H); 2.63 (s, 3H).
Reaction SMILES: FC(F)(F)S([O:6][CH2:7][C@@H:8]1[O:12][CH2:11][C@@H:10]([S:13][C:14](=[O:16])[CH3:15])[CH2:9]1)(=O)=O.[F:19][C:20]1[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:19][C:20]1[CH:25]=[CH:24][C:23]([O:6][CH2:7][C@@H:8]2[O:12][CH2:11][C@@H:10]([S:13][C:14](=[O:16])[CH3:15])[CH2:9]2)=[CH:22][CH:21]=1
Reactant: CC(=O)S[C@@H]1CO[C@@H](COS(=O)(=O)C(F)(F)F)C1
Reactant: Oc1ccc(F)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)S[C@@H]1CO[C@@H](COc2ccc(F)cc2)C1
Yield: 73.7 %

Procedure:
The title compound is prepared by the procedure of Example 23 using 1.49 g of product from Example 22 in 1 ml of methylene chloride, 0.542 g of 4-fluorophenol, 2.5 ml of Hunig's base and 3 ml of methylene chloride to give 0.963 g of the desired compound.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[NH:8]C(=O)[N:6]3[N:13]=[C:14]([CH:16]4[CH2:18][CH2:17]4)[N:15]=[C:5]3[C:4]=2[CH:3]=1.[OH-].[Na+].O.C(O)(=O)C>C(O)CO>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]([NH2:8])=[C:4]([C:5]2[NH:6][N:13]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[N:15]=2)[CH:3]=1
Reactant: O=c1[nH]c2ccc(Cl)cc2c2nc(C3CC3)nn12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: OCCO
Product: Nc1ccc(Cl)cc1-c1nc(C2CC2)n[nH]1
Reaction time: 0.5 h
Yield: 86.7 %

Procedure:
To a well stirred slurry of 9-chloro-2-cyclopropyl-6H-[1,2,4]triazolo[1,5-c]quinazolin-5-one (5.20 g, 19.9 mmol) in ethylene glycol (40 mL) which was heated to 100° C. was added aqueous sodium hydroxide (10 N, 4 mL, 39.9 mmol). The slurry was heated at reflux for 18 h. After cooling, water (25 mL) was added to the resulted suspension and the pH was adjusted to 6-7 by adding glacial acetic acid (CO2-evolution). The slurry was stirred for 30 min. The solid was collected by filtration and washed with water (3×15 mL). Drying (HV) afforded the title compound (4.05 g, 86%) as a light brown solid. MS: m/e=235.0 [M+H]+.
Reaction SMILES: [C:1]([O:13]C)(=O)[C:2]1[CH:11]=[CH:10][C:5](C(OC)=O)=[CH:4][CH:3]=1.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:35]([Cl:38])(Cl)=[O:36].[Cl-:39].C(OC)(=O)C1C=CC(C([O-])=O)=CC=1>>[C:35]([Cl:38])(=[O:36])[C:5]1[CH:10]=[CH:11][C:2]([C:1]([Cl:39])=[O:13])=[CH:3][CH:4]=1
Reactant: COC(=O)c1ccc(C(=O)OC)cc1
Reactant: O=C(Cl)Cl
Reactant: [Cl-]
Agent: COC(=O)c1ccc(C(=O)[O-])cc1
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Product: O=C(Cl)c1ccc(C(=O)Cl)cc1
Reaction time: 5 h

Procedure:
A mixture of 150 g of dimethyl terephthalate and 7 g of triphenylphosphine oxide was gassed with phosgene as in Example 1. After 5 hours, the reaction mixture contained only 1.3% of dimethyl terephthalate and 1.3% of methyl terephthalate chloride. After 6-7 hours, the conversion was complete and terephthalic acid dichloride was obtained (>99% pure).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.[CH2:22](O)[CH3:23]>S(=O)(=O)(O)O>[CH2:22]([O:19][C:18](=[O:20])[C@H:17]([CH3:21])[N:16]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[N:9]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH3:23]
Reactant: C[C@@H](C(=O)O)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)[C@H](C)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Temperature: 25 °C
Yield: 68 %

Procedure:
A suspension of crude (S)-2-(4-chlorophenyl)-α-methyl-3H-imidazo[4,5-b]pyridine-3-acetic acid (2.0 g, 0.00663 mole) in absolute ethanol was stirred at room temperature while 4 drops of concentrated sulfuric acid was added. The reaction mixture was refluxed for three days. Approximately 1/2 to 2/3 of the solvent was removed under reduced pressure. Saturated sodium bicarbonate solution (20 ml) was added to the remaining solution. The product was extracted into two portions of ethyl acetate and the combined organic layers were washed twice with water, dried over sodium sulfate, filtered and evaporated to an oil which was dissolved in hot absolute ethanol. Water was added to the cloud point and upon cooling to room temperature, a solid precipitated. The solid was collected by filtration, rinsed with water and dried under high vacuum at 50° C. to give 1.48 g (68%) of title compound, mp 103°-106° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=2)[CH:9]([CH2:24][CH2:25][CH:26]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[C:10](N2C(C3C=CC=CC=3)COC2=O)=[O:11])=[CH:4][CH:3]=1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.O.O.O.[F-].C([NH+](CCCC)CCCC)CCC.C(O)(=O)C>COC(C)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:42]([C:43]3[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=3)[C:10](=[O:11])[CH:9]2[CH2:24][CH2:25][CH:26]([O:34][Si:35]([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:37])[CH3:36])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)OC(CCC(C(=O)N1C(=O)OCC1c1ccccc1)C(Nc1ccc(F)cc1)c1ccc(Br)cc1)c1ccc(F)cc1
Agent: CCCC[NH+](CCCC)CCCC
Agent: C[Si](C)(C)C(C(N)=O)[Si](C)(C)C
Agent: [F-]
Solvent: COC(C)(C)C
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)[Si](C)(C)OC(CCC1C(=O)N(c2ccc(F)cc2)C1c1ccc(Br)cc1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3.34 g of 3-[2-[(4-bromophenyl)-(4-fluorophenylamino)methyl]-5-(tert-butyl-dimethylsilanyloxy)-5-(4-fluorophenyl)pentanoyl]-4-phenyloxazolidin-2-one are suspended in 70 ml of tert-butyl methyl ether. 3.8 ml of bis(trimethylsilyl)acetamide and 144 mg of tributylammonium fluoride trihydrate are then added. The reaction mixture is stirred at room temperature overnight, and 0.7 ml of glacial acetic acid are then added. The reaction mixture is concentrated using a rotary evaporator and the residue is purified by column chromatography (SiO2; ethyl acetate/heptane 1:4). The product is obtained as a clear oil. C30H34BrF2NO2Si (586) MS (ESI): M+−131