Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[CH2:5][CH:4]([CH2:15][OH:16])[O:3]1.ClCCl.[OH2:20]>C(#N)C>[C:11]([C:10]1[CH:13]=[CH:14][C:7]([N:6]2[CH2:5][CH:4]([C:15]([OH:20])=[O:16])[O:3][C:2]2=[O:1])=[CH:8][CH:9]=1)#[N:12]
Reactant: N#Cc1ccc(N2CC(CO)OC2=O)cc1
Reactant: O
Solvent: CC#N
Solvent: ClCCl
Product: N#Cc1ccc(N2CC(C(=O)O)OC2=O)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
1 g of 4-(2-oxo-5-hydroxymethyloxazolidin-3-yl)benzonitrile [obtainable according to EP 300 272] dissolved in 12 ml of acetonitrile is added at 16° to a solution of 3.6 g of Na dihydrogen phosphate dihydrate, 3.9 g of Na metaperiodate and 36 mg of RuCl3 in 23 ml of water/2.3 ml of dichloromethane. The reaction mixture is stirred at room temperature for 12 h, filtered and given the customary workup. Concentration by evaporation to dryness in vacuo gives 3-(4-cyanophenyl)-2-oxo-5-oxazolidinecarboxylic acid, m.p. 204°.
Reaction SMILES: [CH:1](/[C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:19]=[CH:18]C(C#N)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[CH:2]\[CH2:3][CH2:4][CH3:5].[OH-:20].[K+].Cl.C(O)CO[CH2:26][CH2:27][OH:28]>O>[CH:1](/[C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:19]=[CH:18][C:26]([C:27]([OH:28])=[O:20])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[CH:2]\[CH2:3][CH2:4][CH3:5]
Reactant: OCCOCCO
Reactant: CCC/C=C/[C@H]1CC[C@H](c2ccc(C#N)cc2)CC1
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: O
Product: CCC/C=C/[C@H]1CC[C@H](c2ccc(C(=O)O)cc2)CC1
Temperature: 25 °C

Procedure:
1.1 g of p-[trans-4-(1E-pentenyl)cyclohexyl]benzonitrile were boiled at 180° C. for 16 hours while gassing with argon in 17.5 ml of a 10 percent solution of potassium hydroxide in diethylene glycol. After cooling to room temperature the dark brown reaction mixture was diluted with 20 ml of water, made acid with 25 percent hydrochloric acid and extracted four times with 100 ml of ethylene chloride each time. The organic phases were washed twice with 80 ml of water each time, dried over magnesium suphate and active carbon and concentrated. There were obtained 1.16 g (98%) of p-[trans-4-(1E-pentenyl)cyclohexyl]benzoic acid as beige crystals; Rf-value (toluene/ethyl acetate vol. 3:1) 0.45.
Reaction SMILES: C[O:2][C:3](=[O:30])[C:4]([CH3:29])([O:6][C:7]1[CH:8]=[C:9]([CH:13]2[C:22]([CH3:24])([CH3:23])[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:25]([O:27]C)=[O:26])[CH:19]=3)[NH:14]2)[CH:10]=[CH:11][CH:12]=1)[CH3:5].[OH-].[Na+]>CO.O1CCCC1>[C:3]([C:4]([O:6][C:7]1[CH:8]=[C:9]([CH:13]2[C:22]([CH3:23])([CH3:24])[CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:25]([OH:27])=[O:26])[CH:19]=3)[NH:14]2)[CH:10]=[CH:11][CH:12]=1)([CH3:29])[CH3:5])([OH:30])=[O:2]
Reactant: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1cccc(OC(C)(C)C(=O)OC)c1)N2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(Oc1cccc(C2Nc3ccc(C(=O)O)cc3CC2(C)C)c1)C(=O)O
Yield: 30.1 %

Procedure:
To a solution of methyl 2-(3-(1-methoxy-2-methyl-1-oxopropan-2-yloxy)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (216 mg, 0.52 mmol) in methanol (8 mL) and tetrahydrofuran (8 mL) was added a 1 M solution of sodium hydroxide (7.87 mL). The mixture was stirred and heated to reflux for 1.5 h. The mixture was concentrated, dissolved in water and acidified to pH=4 with 1M hydrochloric acid. The precipitated solid was filtered and redissolved in tetrahydrofuran, and the organic layers were dried over anhydrous magnesium sulfate. After evaporation of the organic solvent, the residue was treated with dichloromethane to afford 60 mg of 2-(3-(2-carboxypropan-2-yloxy)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acid as a white solid. Isolated yield: 30%; MS (ESI+APCI) M+1=384.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH:15]([NH2:18])[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:27][CH2:28][CH2:29][CH2:30]Br>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH:15]([N:18]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:14][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrCCCCBr
Reactant: NC1CCC(CNC(=O)OCc2ccccc2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(NCC1CCC(N2CCCC2)CC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 82.8 %

Procedure:
To a solution of (4-amino-cyclohexylmethyl)-carbamic acid benzyl ester (350 mg, 1.34 mmol) in DMF (5 mL) was added K2CO3 (924 mg, 6.70 mmol) and 1,4-dibromobutane (160 mL, 1.34 mmol). The reaction mixture was stirred at room temperature for 14 h before diluting with EtOAc (100 mL). The reaction solution was washed with water (2×100 mL) and brine before concentrating in vacuo. The residue was purified by chromatography using a 12 g ISCO combi-flash cartridge (silica gel, 95:4.75:0.25 DCM/MeOH/NH4OH) to afford (4-pyrrolidin-1-yl-cyclohexylmethyl)-carbamic acid benzyl ester (351 mg, 83%) as an off-white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[CH2:19]([C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29](O)=[O:30])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O.C(N(CC)CC)C>[CH2:19]([C:26]1[CH:27]=[C:28]([C:29]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)=[O:30])[CH:32]=[CH:33][CH:34]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C(O)c1cccc(Cc2ccccc2)c1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(N)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(NC(=O)c2cccc(Cc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
To a solution of tert-butyl [trans-2-(4-aminophenyl)cyclopropyl]carbamate (100 mg) described in a document (J. Am. Chem. Soc., 2010, 132, 6827.) in acetonitrile (4 mL) were added 3-benzylbenzoic acid (103 mg) described in a document (J. Org. Chem. 2001, 66, 2874.), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (93 mg), 1-hydroxybenzotriazole (65.3 mg) and triethylamine (140 μL). The mixture was stirred at room temperature overnight and water was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was recrystallized (hexane/ethyl acetate) to give the title compound (126 mg).
Reaction SMILES: C1(P(O[C:16]2[C@H:17]([CH3:40])[C@@H:18]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]3[C:20]=2[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])(C2C=CC=CC=2)=O)C=CC=CC=1.[SH:41][C@@H:42]1[CH2:46][N:45]([CH3:47])[C@H:44]([C:48]([N:50]2[CH2:55][CH2:54][N:53]([C:56](=[NH:71])[NH:57][C:58]([O:60][CH2:61][C:62]3[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=3)=[O:59])[CH2:52][CH2:51]2)=[O:49])[CH2:43]1>C(#N)C.C(N(C(C)C)CC)(C)C>[OH:38][C@@H:36]([C@H:35]1[C:34](=[O:39])[N:19]2[C:20]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([N+:31]([O-:33])=[O:32])=[CH:29][CH:30]=3)=[O:22])=[C:16]([S:41][C@@H:42]3[CH2:46][N:45]([CH3:47])[C@H:44]([C:48]([N:50]4[CH2:55][CH2:54][N:53]([C:56](=[NH:71])[NH:57][C:58]([O:60][CH2:61][C:62]5[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=5)=[O:59])[CH2:52][CH2:51]4)=[O:49])[CH2:43]3)[C@H:17]([CH3:40])[C@H:18]12)[CH3:37]
Reactant: CN1C[C@@H](S)C[C@H]1C(=O)N1CCN(C(=N)NC(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@H]12
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CCN(C(=N)NC(=O)OCc5ccc([N+](=O)[O-])cc5)CC4)N(C)C3)[C@H](C)[C@H]12
Reaction time: 8 h
Yield: 76.9 %

Procedure:
1600 mg of 4-nitrobenzyl (1R, 5R,6S)-2-(diphenylphosphoryloxy)-6-[(1R) -1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (prepared as described in Preparation 123) were dissolved in 16 ml of dry acetonitrile, and a solution of 1120 mg of (2S,4S)-4-mercapto-1-methyl-2-[4-(4-nitrobenzyloxycarbonylamidino) piperazin-1-ylcarbonyl]pyrrolidine (prepared as described in Preparation 93) in 11 ml of dry acetonitrile and 430 μl of diisopropylethylamine were added dropwise to the resulting solution, whilst ice-cooling. The resulting mixture was stirred at the same temperature overnight, after which it was concentrated by evaporation under reduced pressure. The resulting residue was diluted with ethyl acetate, and the mixture was washed with an aqueous solution of sodium hydrogencarbonate, with water and with an aqueous solution of sodium chloride, in that order. The ethyl acetate layer was dehydrated over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was subjected to reverse phase silica gel column chromatography (Cosmosil 75C18 -prep, manufactured by Nacalai Tesque, 300 ml), eluted with a 1 by volume mixture of acetonitrile and water. The fractions containing the desired compound were collected and concentrated by evaporation under reduced pressure, to obtain 1520 mg of the title compound, as a powder.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11])C.[Br:19]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C1(=O)NC(=O)CC1>C(Cl)(Cl)(Cl)Cl>[Br:19][CH2:18][C:16]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[C:8]([O:7][CH2:6][CH2:5][CH2:4][O:3][CH3:1])[CH:17]=1
Reactant: CCOCCCOc1cc(C)ccc1C(=O)OC
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1
Solvent: ClC(Cl)(Cl)Cl
Product: COCCCOc1cc(CBr)ccc1C(=O)OC

Procedure:
The mixture of 25.0 g of methyl 2-(3-ethoxypropoxy)-4-methylbenzoate, 18.4 g of N-bromo-succinimide, 1.65 g of 2,2′-azobis(2-methylpropionitrile) and 2.46 g of dibenzoyl peroxide in 1.2 l of carbon tetrachloride is heated to reflux with stirring and stirred over 3 hours (succinimide crystallizes out). The reaction mixture is cooled and clarified by filtration, and the filtrate is concentrated by evaporation. The title compound is obtained as a slightly orange oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.30 (1:1 EtOAc-heptane); Rt=17.10 (II).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH2:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([CH2:18][CH2:19][CH3:20])[S:17][C:10]=12.[C:22]1([CH2:28][C:29]([N:31]=[C:32]=[S:33])=[O:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1(C)C=CC=CC=1.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:32]([NH:31][C:29](=[O:30])[CH2:28][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[S:33])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([CH2:18][CH2:19][CH3:20])[S:17][C:10]=12
Reactant: CCCc1cc2nccc(Oc3ccc(N)cc3F)c2s1
Reactant: O=C(Cc1ccccc1)N=C=S
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCCc1cc2nccc(Oc3ccc(NC(=S)NC(=O)Cc4ccccc4)cc3F)c2s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 55.6 %

Procedure:
A mixture of 3-fluoro-4-(2-propylthieno[3,2-b]pyridin-7-yloxy)benzenamine (8 mg, 0.03 mmol) and 2-phenylethanoyl isothiocyanate (9 mg, 0.05 mmol; prepared according to J. Org. Chem. 1964, 29, 1115-1119) in 1:1 toluene/ethanol (0.5 mL) were stirred at room temperature for 2 hours. The reaction mixture was purified by preparative TLC (5% MeOH/EtOAc). The product was obtained as a waxy solid (8 mg, 58%). 1H NMR (400 MHz, CDCl3) δ 12.49 (s, 1H), 8.57 (s, 1H), 8.45 (m, 1H), 7.94 (m, 1H), 7.44 (m, 4H), 7.32 (m, 2H), 7.25 (m, 2H, overlaps chloroform), 6.48 (m, 1H), 3.76 (s, 2H), 2.93 (m, 2H), 1.81 (m, 2H), 1.04 (m, 3H). LRMS (ESI neg) m/e 478 (M−1).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[CH:15]([CH3:20])[C:16](=O)[CH2:17][CH3:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:22]([NH:24][NH2:25])[CH3:23]>C(#N)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:24]([CH2:22][CH3:23])[N:25]=[C:16]([CH2:17][CH3:18])[C:15]=2[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCNN
Reactant: CCC(=O)C(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Solvent: O
Solvent: CC#N
Product: CCc1nn(CC)c(C2CCN(C(=O)OC(C)(C)C)CC2)c1C
Temperature: 25 °C
Reaction time: 20 h
Yield: 72.2 %

Procedure:
A solution of 1-(t-butoxycarbonyl)-4-(1,3-dioxo-2-(RS)-methylpent-1-yl)piperidine (435 mg, 1.5 mmol) (from Step D) in 2:1 v/v acetonitrile/water (12 mL) was treated with ethylhydrazine (34% sol'n in water, 0.28 mL, 1.6 mmol) and the resulting mixture was stirred at rt for 20 h. The reaction mixture was partitioned between 75 mL of ether and 25 mL of sat'd sodium chloride and the layers were separated. The organic layer was dried over magnesium sulfate and concentrated. MPLC (Biotage) on a 40S silica cartridge using 4:1 v/v, then 1:1 v/v hexanes/ethyl acetate as the eluent afforded 348 mg (74%) of the title compound:
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[C:7]1(OB=O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:17]1[CH:18]=[CH:19][C:20]([C:23]([NH:25][C:26]2[CH:38]=[C:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:36]=[CH:35][C:27]=2[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:24])=[N:21][CH:22]=1>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.O.C(OCC)(=O)C.COCCOC>[C:39]1([C:37]2[CH:36]=[CH:35][C:27]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[C:26]([NH:25][C:23]([C:20]3[CH:19]=[CH:18][C:17]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[CH:22][N:21]=3)=[O:24])[CH:38]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1ccc(Br)cn1
Reactant: O=BOc1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: COCCOC
Solvent: O
Product: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1ccc(-c2ccccc2)cn1
Temperature: 25 °C
Yield: 92.2 %

Procedure:
Sodium carbonate (55 mg), phenylboranic acid (38 mg), water (0.35 mL), and bis(triphenylphosphine)palladium(II) dichloride (3.7 mg) were added to an ethylene glycol dimethyl ether (1.2 mL) suspension of tert-butyl 2-(5-bromopyridine-2-carboxamido)-4-phenylbenzoate (0.12 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then sodium carbonate (55 mg), phenylboranic acid (38 mg), and bis(triphenylphosphine)palladium(II) dichloride (3.7 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and ethyl acetate and water were added thereto. The insoluble substance was removed by filtration. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-80% hexane/ethyl acetate] to obtain 0.11 g of tert-butyl 4-phenyl-2-(5-phenylpyridine-2-carboxamido)benzoate as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:17](=[O:18])[CH:16]3[C:11](=[CH:12][CH2:13][CH2:14][CH2:15]3)[C:10]2=[O:19])=[CH:4][C:3]=1[S:20][C:21]1([C:24](Cl)=[O:25])[CH2:23][CH2:22]1.[CH3:27][OH:28].C(N(CC)CC)C>C(OC)(=O)C>[CH3:27][O:28][C:24]([C:21]1([S:20][C:3]2[CH:4]=[C:5]([N:9]3[C:17](=[O:18])[CH:16]4[C:11](=[CH:12][CH2:13][CH2:14][CH2:15]4)[C:10]3=[O:19])[C:6]([F:8])=[CH:7][C:2]=2[Cl:1])[CH2:23][CH2:22]1)=[O:25]
Reactant: CO
Reactant: O=C1C2=CCCCC2C(=O)N1c1cc(SC2(C(=O)Cl)CC2)c(Cl)cc1F
Solvent: COC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)C1(Sc2cc(N3C(=O)C4=CCCCC4C3=O)c(F)cc2Cl)CC1
Temperature: 25 °C

Procedure:
While stirring at room temperature, a solution of 1 g of 1-[2-chloro-4-fluoro-5-(1,2,3,4,5,6-hexahydro-1,3-dioxo-isoindolyl)-phenylthio]-cyclopropanecarboxylic acid chloride obtained in accordance with Example P9 in 10 ml of methyl acetate is added dropwise to a solution of 10 ml of methanol and 0.5 ml of triethylamine in 10 ml of methyl acetate. After stirring for 3 hours at room temperature, the resulting triethylamine hydrochloride is filtered off and the filtrate is concentrated by evaporation, yielding 0.9 g of 1-[2-chloro-4-fluoro-5-(1,2,3,4,5,6-hexahydro-1,3-dioxo-isoindolyl)-phenylthio]-cyclopropanecarboxylic acid methyl ester having a melting point of from +142° to +144° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[C:5]([N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1O)[CH3:8])=[O:6].[C:20]([O-:23])([O-])=O.[K+].[K+]>CN(C=O)C.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[C:5]([N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:23][CH2:20][CH2:5][N:7]([CH3:9])[CH3:8])[CH3:8])=[O:6]
Reactant: O=C([O-])[O-]
Reactant: CN(C(=O)c1ccc(Cl)c(Br)c1)c1ccccc1O
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)CCOc1ccccc1N(C)C(=O)c1ccc(Cl)c(Br)c1
Yield: 39.9 %

Procedure:
A mixture of 3-bromo-4-chloro-N-(2-hydroxy-phenyl)-N-methyl-benzamide (404 mg, 1.18 mmol, Step 3B), β-dimethylaminobromide hydrobromide (553 mg, 2.38 mmol) and K2CO3 (655 mg, 4.75 mmol) was heated in DMF (7 mL) at 80° C. for 14 hrs. The mixture was then diluted with ethyl acetate and water. The organic layer was separated and washed with water and brine, dried over Na2SO4, then purified by silica gel column chromatography eluting with DCM/MeOH (95/5 with gradient to 9/1) to yield 3-bromo-4-chloro-N-[2-(2-dimethylamino-ethoxy)-phenyl]-N-methyl-benzamide (97 mg). MS [M+H]+: 412.7; tR=2.24 min. (method 1)
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[CH3:9].CN(C)C=O.[N-:15]=[N+:16]=[N-:17].[Na+].C(=O)([O-])[O-].[K+].[K+]>O>[N:15]([CH2:2][CH2:3][N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[CH3:9])=[N+:16]=[N-:17]
Reactant: Cc1nccn1CCCl
Reactant: [N-]=[N+]=[N-]
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nccn1CCN=[N+]=[N-]

Procedure:
To a solution of 8 parts of 1-(2-chloroethyl)-2-methylimidazole (U.S. Pat. No. 3,882,136) in 200 parts of N,N-dimethylformamide is added a slurry of 5 parts of sodium azide in 100 parts of N,N-dimethylformamide. The resultant mixture is stirred for 2 hours at approximately 65°, then cooled and thereupon diluted with 600 parts of water. Sufficient potassium carbonate is added to insure basicity. The mixture thus obtained is extracted with chloroform. The chloroform extract is dried over anhydrous magnesium sulfate and stripped of solvent by vacuum distillation, affording 1-(2-azidoethyl)-2-methylimidazole as the residue. The product has the formula ##SPC4##
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[C:14]([O:21][C@@H:22]3[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]3[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:15][NH:16][C:17]=2[CH:18]([CH3:20])[CH3:19])=[C:8]([CH3:57])[CH:7]=1.[CH2:58]([NH:65][CH2:66][CH2:67][C:68]([NH2:70])=[O:69])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1.[I-].[Na+].Cl>C(#N)C.C(O)C>[CH2:58]([N:65]([CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[C:14]([O:21][C@@H:22]3[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]3[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:15][NH:16][C:17]=2[CH:18]([CH3:20])[CH3:19])=[C:8]([CH3:57])[CH:7]=1)[CH2:66][CH2:67][C:68](=[O:69])[NH2:70])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1
Reactant: NC(=O)CCNCc1ccccc1
Reactant: Cc1cc(OCCCCl)ccc1Cc1c(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)n[nH]c1C(C)C
Agent: Cl
Agent: [I-]
Agent: [Na+]
Solvent: CCO
Solvent: CC#N
Product: Cc1cc(OCCCN(CCC(N)=O)Cc2ccccc2)ccc1Cc1c(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)n[nH]c1C(C)C
Temperature: 70 °C
Reaction time: 48 h
Yield: 61.7 %

Procedure:
A mixture of 4-{[4-(3-chloropropoxy)-2-methylphenyl]-methyl}-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (1.34 g), 3-benzylaminopropionamide (0.73 g), sodium iodide (0.24 g), ethanol (6 mL) and acetonitrile (6 mL) was stirred at 70° C. for 2 days. To the reaction mixture was added sodium iodide (0.2 g), and the mixture was further stirred at 75° C. for 24 hours. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethylacetate. The extract was washed with water, a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/5-dichloromethane/methanol=15/1) to give the title compound (0.97 g).
Reaction SMILES: C1N=CN([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])C=1.[CH2:13]([O:15][C:16]([C:18]1[C:26]2[C:21](=[CH:22][C:23]([Br:31])=[C:24]([CH2:27]C(O)=O)[CH:25]=2)[NH:20][C:19]=1[CH3:32])=[O:17])[CH3:14].CO[C:35]1[CH:36]=[C:37]([CH2:41]CN)[CH:38]=[CH:39][CH:40]=1>C1COCC1>[CH2:13]([O:15][C:16]([C:18]1[C:26]2[C:21](=[CH:22][C:23]([Br:31])=[C:24]([CH2:27][C:6](=[O:7])[NH:8][CH2:9][CH2:10][C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[CH:36]=3)[CH:25]=2)[NH:20][C:19]=1[CH3:32])=[O:17])[CH3:14]
Reactant: COc1cccc(CCN)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCOC(=O)c1c(C)[nH]c2cc(Br)c(CC(=O)O)cc12
Solvent: C1CCOC1
Product: CCOC(=O)c1c(C)[nH]c2cc(Br)c(CC(=O)NCCc3cccc(C)c3)cc12
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 84 %

Procedure:
To a solution of CDI (0.93 g, 5.7 mmol) in THF (50 mL) is added a solution of 6-bromo-5-carboxymethyl-2-methyl-1H-indole-3-carboxylic acid ethyl ester in THF (50 mL). The mixture is stirred at room temperature for 45 minutes, then refluxed for 1 hour. After cooling the reaction mixture to room temperature, 2-(3-methoxyphenyl)ethylamine is added and resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is concentrated in vacuo, ethyl acetate (150 mL) is added, then washed with 1N HCl (50 mL), 1N NaOH (50 mL), and brine (50 mL). The organic layer is dried (Na2SO4) and concentrated in vacuo to give the desired product (2.15 g, 84%). MS: 473, 475 (M+1)+.
Reaction SMILES: [O:1]=[Sb:2]([O:4][Sb:5](=[O:7])=[O:6])=[O:3].[N+]([O-])([O-])=[O:9].[In+3:12].[N+]([O-])([O-])=[O:14].[N+]([O-])([O-])=O.N>O>[OH-:1].[In+3:12].[OH-:9].[OH-:14].[O:1]=[Sb:2]([O:4][Sb:5](=[O:7])=[O:6])=[O:3]
Reactant: O=[N+]([O-])[O-]
Agent: N
Agent: O=[Sb](=O)O[Sb](=O)=O
Agent: [In+3]
Solvent: O
Product: [OH-]
Temperature: 25 °C

Procedure:
300 g of water was added to 600 g of the diantimony pentoxide sol (specific gravity: 1.198, Sb2O5 concentration: 18.4 wt %) prepared in Preparation Example 1 for dilution. Then, an aqueous indium nitrate solution having 242.2 g of indium nitrate (In(NO3)3.3H2O, In2O3 content: 39.1 wt %, guaranteed reagent, manufactured by Mitsuwa Kagaku Yakuhin K. K.) dissolved in 241.5 g of water, was added thereto with stirring at room temperature. Then,.the mixture was heated to 90° C. and maintained at that temperature for 10 hours. Then, 125.8 g of 28% aqueous ammonia (guaranteed reagent) was added thereto to adjust the pH of the slurry to 7.05, to obtain a mixed slurry of indium hydroxide and diantimony pentoxide. This slurry had an In2O3 concentration of 6.27 wt %, a Sb2O5 concentration of 7.31 wt % and an In2O3 /Sb2O5 molar ratio of 1.0.