Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][NH:9][C:10](=[O:18])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1N.N([O-])=O.[Na+]>C(O)C.Cl.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([OH:18])=[N:9]1
Reactant: Nc1ccccc1C(=O)NNc1ccccc1F
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Oc1nn(-c2ccccc2F)c2ccccc12
Temperature: 55 °C
Reaction time: 3 h
Yield: 94 %

Procedure:
A stirred suspension of 105 g (0.429 mole) of 2-amino-benzoic acid N′-(2-fluoro-phenyl)-hydrazide in 1250 mL of ethanol and 1250 mL of 1N hydrochloric acid was heated to 55° C. A solution of 59 g (0.858 mole) of sodium nitrite in 200 mL of water was added dropwise over a 30 minute period. Approximately 10 minutes into the addition a solid began separating. External heating was continued until the reaction temperature reached 65° C. and then it was turned off. The temperature remained at 65-68° C. during the addition and gas evolution became vigorous approximately halfway through the addition. Toward the end of the addition, gas evolution slowed and the temperature dropped below 65° C. External heating was reapplied and the mixture was stirred at 70° C. for 3 hours. The mixture was cooled to −10° C. and filtered. The solid was rinsed once with 50 mL of ethanol, then once with 100 mL of water, and pressed dry under suction. Further drying in vacuo at 35° C. for 7 hours afforded 92 g (94%) of product.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[C:14]([O:16]C)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@@H]1C[C@H](F)CN1C(=O)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1C[C@@H](F)C[C@H]1C(=O)O
Yield: 82.9 %

Procedure:
Methyl(2S,4S)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylate (5.00 g) was dissolved in methanol (30 mL). While stirring this solution under ice cooling, 5 mol/L aqueous sodium hydroxide (12 mL) was gradually added dropwise. After stirring at room temperature for 2 hours, the reaction mixture was evaporated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, diluted with 10% aqueous potassium bisulfate (70 mL), and then extracted with ethyl acetate. The extracted solution was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. Diisopropyl ether (20 mL) was added to the resulting residue and the precipitated crystal was collected by filtration to give the titled compound (3.91 g, white powder).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:35][C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[C:14]([NH:35][C:36]3[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=3)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)C(C1CCCCC1)n1c(-c2ccc(Cl)cc2)nc2cc(F)c(F)cc21
Reactant: N#Cc1ccc(N)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N#Cc1ccc(NC(=O)C(C2CCCCC2)n2c(-c3ccc(Cl)cc3)nc3cc(F)c(F)cc32)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 71.9 %

Procedure:
To the suspension of 0.5 g (1.24 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid (Ex. 22, int. c) in 3 ml dichloromethane 0.01 ml (0.12 mmol) N,N-dimethylformamide, 0.13 ml (1.54 mmol) oxalylchloride were added dropwise under gas evolution. The resulting clear, light yellow solution was stirred for 1 h at room temperature, then evaporated to dryness, treated twice with 5 ml of dichloromethane and again evaporated to dryness. The light yellow solid was dissolved in 8 ml of dichloromethane and added dropwise to a stirred mixture of 0.13 g (1.24 mmol) 4-aminobenzonitrile and 0.46 ml (3.31 mmol) triethylamine in dichloromethane. After stirring for 3.75 h the clear yellow solution was poured on water and extracted twice with dichloromethane. The organic layers were washed with water and brine, dried over magnesium sulfate, filtered and after addition of silica gel evaporated to dryness. Purification by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane to heptan/ethyl acetate (1:0 to 1:1 v/v) yielded 0.45 g (81%) of the title compound as a light brown solid. MS (ES−): M−H: 571.2.
Reaction SMILES: Cl[C:2]1[C:3](=[O:15])[N:4]([C@H:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=1.[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([Cl:26])[CH:25]=1)[NH:22][CH2:21][CH2:20]2>>[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([Cl:26])[CH:25]=1)[N:22]([C:2]1[C:3](=[O:15])[N:4]([C@H:9]([CH2:12][O:13][CH3:14])[CH2:10][CH3:11])[CH:5]=[C:6]([Cl:8])[N:7]=1)[CH2:21][CH2:20]2
Reactant: Clc1cc(Br)cc2c1NCC2
Reactant: CC[C@@H](COC)n1cc(Cl)nc(Cl)c1=O
Product: CC[C@@H](COC)n1cc(Cl)nc(N2CCc3cc(Br)cc(Cl)c32)c1=O

Procedure:
Prepared in a similar fashion as described for Example 413 using 3,5-dichloro-1-[(1S)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone and 5-bromo-7-chloroindoline as the starting materials. mp 121–122° C.; 1H NMR (300 MHz, CDCl3): δ 7.24 (s, 1 H), 7.18 (s, 1 H), 6.99 (s, 1 H), 4.90–4.80 (m, 1 H), 4.26 (t, J=8.1 Hz, 2 H), 3.60 (dd, J=10.2, 5.5 Hz, 1 H), 3.49 (dd, J=10.6, 3.3 Hz, 1 H), 3.28 (s, 3 H), 3.06 (t, J=8.1 Hz, 2 H), 1.83–1.65 (m, 2 H), 0.86 (t, J=7.4 Hz, 3 H); HRMS (ESI) calcd for C17H19N3O2BrCl2 (M+H)+: 446.0038; Found m/z 446.0048.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([C:11]([F:14])([F:13])[F:12])=[CH:4][N:3]=1.[OH-].[Na+].O.C(OCC)(=O)C.[CH:24]([C:36]([O:38][CH2:39][CH3:40])=[O:37])([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>O1CCCC1>[N+:8]([C:7]1[C:2]([C:24]([C:36]([O:38][CH2:39][CH3:40])=[O:37])([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[N:3][CH:4]=[C:5]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)([O-:10])=[O:9]
Reactant: CCOC(=O)CC(C(=O)OCC)C(=O)OCC
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cnc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)CC(C(=O)OCC)(C(=O)OCC)c1ncc(C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 1.8 g of 2-chloro-3-nitro-5-(trifluoromethyl)pyridine in 8 mL of tetrahydrofuran, 2.0 mL of triethyl 1,1,2-ethanetricarboxylate and 0.63 g of 60% sodium hydroxide were added under cooling with ice, and the mixture was stirred at room temperature for 2 hours. Thereto were added water and ethyl acetate, the organic layer was separated, and washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 3.5 g of triethyl 1-(3-nitro-5-(trifluoromethyl)pyridin-2-yl)ethane-1,1,2-tricarboxylate as a brown oily substance.
Reaction SMILES: C[Sn](C)(C)[C:3]1[CH:4]=[C:5]2[CH2:11][C@:10]3([CH:16]4[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]4)[CH2:12]3)[O:9][C:6]2=[N:7][CH:8]=1.FC(F)(F)S(O[C:27]1[C:35]2[C:30](=[N:31][CH:32]=[CH:33][CH:34]=2)[O:29][CH:28]=1)(=O)=O>>[O:29]1[C:30]2=[N:31][CH:32]=[CH:33][CH:34]=[C:35]2[C:27]([C:3]2[CH:4]=[C:5]3[CH2:11][C@:10]4([CH:16]5[CH2:17][CH2:18][N:13]([CH2:14][CH2:15]5)[CH2:12]4)[O:9][C:6]3=[N:7][CH:8]=2)=[CH:28]1
Reactant: O=S(=O)(Oc1coc2ncccc12)C(F)(F)F
Reactant: C[Sn](C)(C)c1cnc2c(c1)C[C@@]1(CN3CCC1CC3)O2
Product: c1cnc2occ(-c3cnc4c(c3)C[C@@]3(CN5CCC3CC5)O4)c2c1

Procedure:
Prepared by a method analogous to that described for the preparation of Example 1 from (2′R)-5′-trimethylstannyl-spiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] and furo[2,3-b]pyridin-3-yl trifluoromethanesulfonate. The title compound was obtained as a colourless solid; m/e 334 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([OH:11])=[O:10])=[N+:6]([O-:8])[CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([O:11][CH3:16])=[O:10])=[N+:6]([O-:8])[CH:7]=1
Reactant: CO
Reactant: O=C(O)c1ccc(Br)c[n+]1[O-]
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(Br)c[n+]1[O-]

Procedure:
To a solution of 5-bromo-2-carboxypyridine 1-oxide (19.6 g) in methanol (300 mL) was added dropwise thionyl chloride (37.1 g) at 0° C., and the mixture was heated under reflux for 1 hr. The reaction mixture was concentrated under reduced pressure and the residue was washed with ethyl acetate to give the title compound (22.0 g) as white crystals. This compound was used for the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:14]([C@H:17]2[C@H:22]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@@H:21]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@H:20]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C@@H:19]([CH2:47][O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[O:18]2)=[CH:13][C:3]=1[CH2:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.CC#N.[CH:59]1([NH2:62])[CH2:61][CH2:60]1.[BH3-]C#N.[Na+]>C(Cl)Cl.C(O)(=O)C>[Cl:1][C:2]1[CH:16]=[CH:15][C:14]([C@H:17]2[C@H:22]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@@H:21]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@H:20]([O:39][CH2:40][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C@@H:19]([CH2:47][O:48][CH2:49][C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[O:18]2)=[CH:13][C:3]=1[CH2:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:62][CH:59]2[CH2:61][CH2:60]2)=[CH:7][CH:6]=1
Reactant: NC1CC1
Reactant: O=Cc1ccc(Cc2cc([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)ccc2Cl)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC#N
Solvent: CC(=O)O
Solvent: ClCCl
Product: Clc1ccc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1Cc1ccc(CNC2CC2)cc1
Reaction time: 0.5 h

Procedure:
A solution of 4-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)benzyl)benzaldehyde (intermediate AP) (40 mg) in CH2Cl2:CH3CN (v/v=1:1) (1.0 mL) was cooled to 0° C., followed by addition of cyclopropylamine (15 mg) and acetic acid (1 mg). After 30 min, NaBH3CN (17 mg) was added. The reaction was monitored by LC-MS. After the starting material was consumed, ethyl acetate (20 mL) and water (5 mL) were added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic extracts were combined and washed with brine. Removal of ethyl acetate under reduced pressure and purification of the crude product by preparative TLC gave intermediate AQ (30 mg). MS ESI (m/z): 794 (M+H)+.
Reaction SMILES: [CH3:1][SiH:2]1[O:9][Si:8]([CH3:11])([CH3:10])[O:7][Si:6]([CH3:13])([CH3:12])[O:5][Si:4]([CH3:15])([CH3:14])[O:3]1.CCCCCCC.[Cl:23]Cl>>[Cl:23][Si:2]1([CH3:1])[O:3][Si:4]([CH3:14])([CH3:15])[O:5][Si:6]([CH3:13])([CH3:12])[O:7][Si:8]([CH3:11])([CH3:10])[O:9]1
Reactant: ClCl
Reactant: C[SiH]1O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1
Solvent: CCCCCCC
Product: C[Si]1(C)O[Si](C)(C)O[Si](C)(Cl)O[Si](C)(C)O1
Temperature: 0 °C
Yield: 100 %

Procedure:
To a 1000 mL three-necked round bottom flask equipped with a magnetic stirring bar, a thermometer, an inlet for gases and an outlet fitted with a drying tube, was charged the following: 37.17 g (77.87 mmol) of heptamethylcyclotetrasiloxane (59.2% in octamethylcyclotetrasiloxane) and 521.9 g (5214 mmol) of heptane. The mixture was cooled in an ice bath to 0° C. Chlorine (Cl2) was bubbled through the stirred mixture at a rate such that the temperature did not rise above 10° C. The addition of the chlorine was continued until a persistent yellow color, accompanied by a drop in temperature, was observed. Nitrogen gas was bubbled through the solution to remove the HCl generated in the reaction and the excess Cl2. A yield of 100% under anhydrous conditions was determined by gas chromatographic analysis.
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12].F[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25]>>[CH3:23][C:20]1[CH:21]=[CH:22][C:17]([NH:1][C:2]2[S:6][C:5]3[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=3[C:3]=2[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:18]([N+:24]([O-:26])=[O:25])[CH:19]=1
Reactant: Cc1ccc(F)c([N+](=O)[O-])c1
Reactant: CCOC(=O)c1c(N)sc2ccccc12
Product: CCOC(=O)c1c(Nc2ccc(C)cc2[N+](=O)[O-])sc2ccccc12
Yield: 100.9 %

Procedure:
In the same manner as in Starting Material Synthesis Example 4 and using ethyl 2-aminobenzo[b]thiophene-3-carboxylate (4.0 g), 4-fluoro-3-nitrotoluene (3.3 g) and dimethyl sufoxide (55 ml), ethyl 2-(4-methyl-2-nitroanilino)benzo[b]thiophene-3-carboxylate (6.5 g) was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7]O[C:9]2=[O:14])([O-:3])=[O:2].Cl.[CH3:16][S:17]([CH2:20][CH2:21][NH2:22])(=[O:19])=[O:18].CO>>[CH3:16][S:17]([CH2:20][CH2:21][N:22]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[CH:13][C:4]=2[N+:1]([O-:3])=[O:2])[C:9]1=[O:14])(=[O:19])=[O:18]
Reactant: O=c1occc2c([N+](=O)[O-])cccc12
Reactant: CS(=O)(=O)CCN
Agent: Cl
Solvent: CO
Product: CS(=O)(=O)CCn1ccc2c([N+](=O)[O-])cccc2c1=O
Temperature: 25 °C

Procedure:
Into a round bottom flask was combined 5-nitro-isochromen-1-one (1.5 g, 0.0071 mol), 2-(methylsulfonyl)ethanamine hydrochloride (2.2 g, 0.014 mol) and methanol (45 mL, 1.1 mol). The mixture was heated at reflux for 1.5 hours. The mixture was cooled to room temperature and was concentrated to yield a yellow solid. The solid was taken onto the next step without further purification.
Reaction SMILES: Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][C:5]([NH:8]N)=[CH:4][CH:3]=1.Br[CH2:12][C:13]#[N:14].C(N(CC)CC)C.Cl.[CH3:23][N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]1>C(O)C>[CH3:23][N:24]1[CH2:29][CH2:28][C:27]2[N:8]([CH2:12][C:13]#[N:14])[C:5]3[CH:4]=[CH:3][C:2]([CH3:10])=[CH:7][C:6]=3[C:26]=2[CH2:25]1
Reactant: Cc1ccc(NN)cc1
Reactant: N#CCBr
Reactant: CN1CCC(=O)CC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: Cc1ccc2c(c1)c1c(n2CC#N)CCN(C)C1
Yield: 44.2 %

Procedure:
Preparation of the title compound was carried out according to General Method 8 by using p-tolylhydrazine hydrochloride (10 g, 63 mmol), bromo acetonitrile (7.56 ml, 63 mmol), triethylamine (19.1 g, 189 mmol) and N-methyl-4-piperidone hydrochloride (2.54 g, 17 mmol) in ethanol (30 ml) to obtain 1.8 g of 2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)acetonitrile after purification on neutral alumina chromatography eluting with methanol-dichloromethane gradient. The TFA salt of this material was obtained by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL).
Reaction SMILES: [P:1]([O-:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3][CH3:4].[Na+].Br[CH2:11][C:12]1([CH2:20]Br)[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[O:14][CH2:13]1.[Cl-].[NH4+]>C1COCC1.CN(C=O)C>[CH2:3]([O:2][P:1]([CH2:11][C:12]1([CH2:20][P:1]([O:5][CH2:6][CH3:7])([O:2][CH2:3][CH3:4])=[O:8])[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[O:14][CH2:13]1)([O:5][CH2:6][CH3:7])=[O:8])[CH3:4]
Reactant: CCOP([O-])OCC
Reactant: CC1(C)OCC(CBr)(CBr)CO1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCOP(=O)(CC1(CP(=O)(OCC)OCC)COC(C)(C)OC1)OCC
Temperature: 68 °C
Reaction time: 15 h
Yield: 71.3 %

Procedure:
Sodium diethyl phosphite (63.6 g, 400 mmol, 6.0 eq.) was added to a solution of 5,5-di(bromomethyl)-2,2-dimethyl-1,3-dioxane (20.0 g, 66 mmol) in an anhydrous mixture of THF/DMF (9:1, 600 ml). The reaction mixture was stirred for 15 h at 68° C. and subsequently mixed with a saturated aqueous solution of ammonium chloride (20.0 ml) and the volatile constituents were removed in vacuo. The residue was diluted with deionized water (200 ml) and the solution formed was extracted with methylene chloride (3×200 ml). The combined organic phases were dried with anhydrous sodium sulphate and the solvent was then removed under reduced pressure. The obtained crude product was purified by flash column chromatography (eluent: ethyl acetate/methanol 9:1). 19.6 g (71% yield) of the product was obtained as a colorless oil.
Reaction SMILES: [C:1]1([NH:7][C:8]2C=N[C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[CH3:30]COCC>>[I-:18].[CH:24]1([CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][N+:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:30]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:8]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: c1ccc(Nc2cnc3ccccc3c2)cc1
Reactant: ICCCCCc1ccccc1
Reactant: CCOCC
Product: [I-]
Product: c1ccc(-c2cc3ccccc3[n+](CCCCCC3CCCCC3)c2)cc1
Temperature: 25 °C

Procedure:
A solution of Phenyl-quinolin-3-yl-amine (100 mg, 0.45 mmol) toluene (2 ml) and 5-iodo-pentyl-benzene (373 mg, 1.36 mmol) in a sealed pressure tube was stirred at 110° C. for 24 hours. The reaction mixture was cooled to room temperature, diluted with Et2O (15 ml) and the precipitated compound was filtered and washed with Et2O (3×20 ml). The crude product was purified on a chromatographic column using methanol as an eluent to yield a pure product as an orange solid (75 mg, mp 140-141° C.). 1H NMR (CD3OD): δ 1.42-1.56 (m, 2H), 1.66-178 (m, 2H), 2.04-2.18 (m, 2H), 2.58-2.68 (t, 2H, J=7.2 Hz), 4.88-5.04 (t, 2H, J=7.8 Hz), 7.08-7.24 (m, 6H), 7.14 (dd, 2H, J=0.9, 7.5 Hz), 7.40-7.44 (t, 2H, J=8.4 Hz), 7.76-7.84 (t, 1H, J=7.5 Hz), 7.86-7.94 (m, 1H), 8.08 (d, 1H, J=8.4 Hz), 8.30 (d, 1H, J=9.0 Hz), 8.46 (d, 1H, J=2.4 Hz), 9.04 (d, 1H, J=2.7 Hz). Anal Calcd for: C26H27IN2.1H2O: C, 60.92; H, 5.70; N, 5.47. Found: C, 60.79; H, 5.33; N, 6.38.
Reaction SMILES: CI.[Cl:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:7][NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]3[NH:23][N:22]=[N:21][N:20]=3)[CH:17]=2)[C:12]([N:24]2[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26][CH2:25]2)=[N:11][N:10]=1.[C:36](=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:7][NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]3[N:23]([CH3:36])[N:22]=[N:21][N:20]=3)[CH:17]=2)[C:12]([N:24]2[CH2:25][CH2:26][CH:27]([OH:30])[CH2:28][CH2:29]2)=[N:11][N:10]=1
Reactant: O=C([O-])[O-]
Reactant: COc1ccc(CNc2nnc(N3CCC(O)CC3)c3ccc(-c4nnn[nH]4)cc23)cc1Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CI
Product: COc1ccc(CNc2nnc(N3CCC(O)CC3)c3ccc(-c4nnnn4C)cc23)cc1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 19.4 %

Procedure:
0.037 ml methyl iodide was added to a mixture of 0.25 g 1-[4-[(3-chloro-4-methoxybenzyl)amino]-6-(1H-1,2,3,4-tetrazole-5-yl)-1-phthalazinyl]-4-piperidinol, 1.2 g potassium carbonate and 5 ml dimethylformamide, and stirred at room temperature for 3 hr. Water was added to the reaction solution, and the precipitated insoluble matters were collected by filtration. Then, purified by silica gel column chromatography to give 50 mg of the title compound.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[CH:12]1([C:15]2[NH:19][N:18]=[C:17]([NH2:20])[CH:16]=2)[CH2:14][CH2:13]1.C(N(C(C)C)CC)(C)C>C(#N)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:20][C:17]2[CH:16]=[C:15]([CH:12]3[CH2:14][CH2:13]3)[NH:19][N:18]=2)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Reactant: Nc1cc(C2CC2)[nH]n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=[N+]([O-])c1cnc(Cl)nc1Nc1cc(C2CC2)[nH]n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 72.6 %

Procedure:
A mixture of 2,4-dichloro-5-nitropyrimidine (2 g) and 5-cyclopropyl-1H-pyrazol-3-amine (2 g) in acetonitrile (20 mL) with diisopropylethylamine (2 mL) was stirred at room temperature for 24 hours, The resulting mixture was concentrated, and the resulting residue was separated by silica gel column (Hexane/Ethyl acetate) to afford 2.1 g desired product. MS (electrospray): 281 (M+1) for C10H9ClN6O2.
Reaction SMILES: [O-:1][Cr:2]([O:5][Cr]([O-])(=O)=O)(=[O:4])=[O:3].[Na+:10].[Na+].ClCl>[V]>[OH2:1].[OH2:1].[OH2:1].[OH2:1].[Cr:2]([O-:5])([O-:4])(=[O:3])=[O:1].[Na+:10].[Na+:10]
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: [V]
Agent: ClCl
Agent: [Na+]
Product: O
Product: O=[Cr](=O)([O-])[O-]

Procedure:
A process for preparing sodium bichromate substantially free of vanadium and chlorine which comprises concentrating a sodium chromate liquor obtained from chrome-bearing minerals to form crystals of sodium chromate tetrahydrate, separating the tetrahydrate crystals from the liquor and recovering the crystals, treating the separated crystals with sulfuric acid to form the bichromate and recovering the sodium bichromate after separation of insoluble sodium sulfate formed.
Reaction SMILES: C([O:5]O)(C)(C)C.[Cl:7][C:8]1[CH:13]=[C:12]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([S:23][CH3:24])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:11]=[CH:10][C:9]=1[NH:25][C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[Cl:7][C:8]1[CH:13]=[C:12]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:24])=[O:5])=[CH:19][CH:18]=2)(=[O:15])=[O:16])[CH:11]=[CH:10][C:9]=1[NH:25][C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:30])([F:31])[F:29]
Reactant: CSc1ccc(S(=O)(=O)c2ccc(NC(=O)[C@@](C)(O)C(F)(F)F)c(Cl)c2)cc1
Reactant: CC(C)(C)OO
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CS(=O)c1ccc(S(=O)(=O)c2ccc(NC(=O)[C@@](C)(O)C(F)(F)F)c(Cl)c2)cc1
Temperature: 25 °C
Reaction time: 64 h

Procedure:
t-Butylhydroperoxide (0.36 ml of a 3M solution in toluene) was added to a solution of (R)-N-{2-chloro-4-[4-(methylsulphanyl)phenylsulphonyl]phenyl}-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 2) (0.247 g) and d-10-camphorsulphonic acid (0.012 g) in chloroform (5 ml) and the mixture was stirred at ambient temperature for 64 hours. The reaction mixture was transferred directly to a silica gel Mega Bond Elut column and eluted with 0-80% ethyl acetate/hexane to give the title compound (0.237 g) as a foam. NMR (CDCl3): 1.74 (s, 3H), 2.74 (s, 3H), 4.2 (brs, 1H), 7.79 (d, 2H), 7.89 (dd, 1H), 8.0 (m, 1H), 8.1 (d, 2H) 8.65 (d, 1H), 9.38 (brs, 1H); MS (ESP−): 468; EA: found: C, 43.3; H, 3.1; N, 2.98%; C17H15ClF3NO5S2 requires: C, 43.3; H, 3.1; N, 2.8%.
Reaction SMILES: [OH-].[K+].[CH3:3][S:4]([NH:7][C:8]1[S:9][CH:10]=[C:11]([CH2:13][C:14]([O:16]CC)=[O:15])[N:12]=1)(=[O:6])=[O:5].C(OCC)(=O)C>O>[CH3:3][S:4]([NH:7][C:8]1[S:9][CH:10]=[C:11]([CH2:13][C:14]([OH:16])=[O:15])[N:12]=1)(=[O:5])=[O:6]
Reactant: CCOC(=O)Cc1csc(NS(C)(=O)=O)n1
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: CS(=O)(=O)Nc1nc(CC(=O)O)cs1
Yield: 73 %

Procedure:
To a solution of potassium hydroxide (2.9 g.) in water (80 ml.) was added ethyl 2-methanesulfonamidothiazol-4-ylacetate (9.1 g.) under ice-cooling and stirring, and the mixture was stirred for 1 hour at room temperature. After the reaction, to the reaction mixture was added a mixture of water and ethyl acetate, and then the aqueous layer was separated. The remaining ethyl acetate layer was extracted twice with 10% hydroxide aqueous solution. The extracts were combined with the above obtained aqueous layer, and the mixture was acidified with hydrochloric acid under ice-cooling. The precipitated crystals were collected by filtration, washed with water and dried to give 2-methanesulfonamidothiazol-4-ylacetic acid (5.94 g.), mp 158°-160° C. (dec.).