Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=O.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]1[C:22]1[CH:23]=[CH:24][C:25]([O:29][CH3:30])=[C:26]([NH2:28])[CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(=O)C>[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]1[C:22]1[CH:23]=[CH:24][C:25]([O:29][CH3:30])=[C:26]([NH:28][CH2:5][C:4]2[CH:7]=[CH:8][C:9]([N+:10]([O-:12])=[O:11])=[C:2]([OH:1])[CH:3]=2)[CH:27]=1
Reactant: COc1ccc(-c2cc3ccccc3[nH]2)cc1N
Reactant: O=Cc1ccc([N+](=O)[O-])c(O)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1ccc(-c2cc3ccccc3[nH]2)cc1NCc1ccc([N+](=O)[O-])c(O)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64.2 %

Procedure:
3-Hydroxy-4-nitrobenzaldehyde (0.334 g, 2.0 mmol) was added to a stirred mixture of 5-(1H-indol-2-yl)-2-methoxy-phenylamine (0.476 g, 2.0 mmol) in methylene chloride (125 mL), followed by acetic acid (0.2 g). The resulting mixture is stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (0.46 g, 2.2 mmol) was added in one portion, and the resulting homogeneous solution was stirred at room temperature for 3 days. Saturated aqueous sodium bicarbonate solution (100 mL) was added and the mixture is stirred for 2 hours. The mixture was shaken, the organic layer was separated and dried over Na2SO4. The solvent was evaporated to give a brown gum. Recrystallization from methanol gave the product (500 mg), mp 134-135° C.
Reaction SMILES: C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[CH:27]2[CH2:29][CH2:28]2)[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:31])[C:18](=[O:30])[NH:19][N:20]=2)[CH2:9]1)=O)(C)(C)C.[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>C(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[NH:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[CH:27]2[CH2:28][CH2:29]2)[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:31])[C:18](=[O:30])[NH:19][N:20]=2)[CH2:11]1
Reactant: CC1C(=O)NN=C2COc3cc(C4CC4)c(OC4CN(C(=O)OC(C)(C)C)C4)cc3N21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1C(=O)NN=C2COc3cc(C4CC4)c(OC4CNC4)cc3N21
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
To a solution of 3-(7-cyclopropyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yloxy)-azetidine-1-carboxylic acid tert-butyl ester (0.029 g, 0.068 mmol) in DCM (2 mL) was added TFA (0.35 mL) dropwise and the mixture was stirred at ambient temperature for 2 h. The solvent was removed in vacuo to give 6-(azetidin-3-yloxy)-7-cyclopropyl-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one trifluoroacetic acid as a white solid (0.020 g, 90%). LC/MS (Table 1, Method 5) Rt=2.056 min.; MS m/z: 329 [M+H]+.
Reaction SMILES: C1(=O)[N:5]([C@@H:6]2[CH2:15][C@H:14]([OH:16])[C@@H:13]([CH2:17][OH:18])[O:12][C@H:7]2[O:8][CH2:9][CH:10]=[CH2:11])[C:4](=[O:19])[C:3]2=CC=CC=C12.C(N)CCC>CO>[C:4]([NH:5][C@@H:6]1[CH2:15][C@H:14]([OH:16])[C@@H:13]([CH2:17][OH:18])[O:12][C@H:7]1[O:8][CH2:9][CH:10]=[CH2:11])(=[O:19])[CH3:3]
Reactant: C=CCO[C@@H]1O[C@H](CO)[C@@H](O)C[C@H]1N1C(=O)c2ccccc2C1=O
Solvent: CCCCN
Solvent: CO
Product: C=CCO[C@@H]1O[C@H](CO)[C@@H](O)C[C@H]1NC(C)=O
Reaction time: 3 h
Yield: 54 %

Procedure:
A mixture of allyl 2,3-dideoxy-2-phthalimido-β-D-glucopyranoside, Compound 22, (100 mg, 0.30 mmol) and BuNH2 (4 mL) in MeOH (20 mL) was refluxed for 10 hours, then cooled and evaporated. Acetic anhydride (2 mL) was added to a solution of the residue in MeOH (10 mL) at 0°-5° C., and the mixture was stirred for three hours at 0°-5° C. The mixture was concentrated, and the residue was triturated in MeOH with Et2O to give Compound 1i (40 mg, 54 percent).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH:21]([N:23](C1CCCCO1)[OH:24])[CH3:22].[C@@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CO>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH:21]([NH:23][OH:24])[CH3:22]
Reactant: CSc1ccc(/C=C2/C(C)=C(C(C)N(O)C3CCCCO3)c3cc(F)ccc32)cc1
Agent: CC1(C)C2CC[C@]1(CS(=O)(=O)O)C(=O)C2
Solvent: CO
Product: CSc1ccc(/C=C2/C(C)=C(C(C)NO)c3cc(F)ccc32)cc1

Procedure:
The amine intermediate from Step 2 was heated to 50° C. in methanol (20 mL) containing (1R)-(-)-10-camphorsulfonic acid (200 mg) for 18 hours. After quenching with brine the mixture was extracted with ether (100 mL). The crude material was chromatographed on silica gel eluting with a 1:5 mixture of ethyl acetate-hexane to collect the least polar of the two main components of the mixture. This afforded the title compound as a yellow filmy residue which was taken into the next step.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][O:8][C:9]2=O)=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1.[NH3:16]>CO>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:16][C:9]2=[O:8])=[C:4]([N+:13]([O-:15])=[O:14])[CH:3]=1
Reactant: N
Reactant: O=c1occc2c([N+](=O)[O-])cc(Br)cc12
Solvent: CO
Product: O=c1[nH]ccc2c([N+](=O)[O-])cc(Br)cc12
Temperature: 60 °C
Reaction time: 8 h
Yield: 83 %

Procedure:
A sealed tube containing 7-bromo-5-nitro-1H-isochromen-1-one (293a, 9.20 g, 34.1 mmol) and 7 N ammonia solution in methanol (100 mL) was stirred at 60° C. overnight. After chilling in an ice bath, the resulting precipitate was collected by filtration, washed with cold methanol, and air-dried to give 7-bromo-5-nitroisoquinolin-1(2H)-one (293b, 7.6 g, 83% yield). as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 11.82 (br. s., 1H), 8.56-8.64 (m, 2H), 7.48 (d, J=7.58 Hz, 1H), 6.89 (d, J=7.58 Hz, 1H). MS: 267/269 [M−1].
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[CH2:3][CH:4]([C:15]1[CH:22]=[CH:21][C:18]([O:19][CH3:20])=[CH:17][CH:16]=1)[C:5](=[O:14])[C:6]1[CH:13]=[CH:12][C:9]([O:10][CH3:11])=[CH:8][CH:7]=1.[CH2:25]([Mg]I)[CH2:26][CH3:27]>>[CH3:11][O:10][C:9]1[CH:8]=[CH:7][C:6]([C:5]([CH2:25][CH2:26][CH3:27])([OH:14])[CH:4]([CH2:3][C:2]([F:23])([F:24])[F:1])[C:15]2[CH:22]=[CH:21][C:18]([O:19][CH3:20])=[CH:17][CH:16]=2)=[CH:13][CH:12]=1
Reactant: CCC[Mg]I
Reactant: COc1ccc(C(=O)C(CC(F)(F)F)c2ccc(OC)cc2)cc1
Product: CCCC(O)(c1ccc(OC)cc1)C(CC(F)(F)F)c1ccc(OC)cc1

Procedure:
To an ethereal solution of n-propyl magnesium iodide (prepared from 0.07 molar n-propyl iodide and magnesium in 100 ml. ether) was added, while stirring, a solution of 16.9 g. (0.05 mole) α-trifluoroethyl-deoxyanisoin (see Example 1a)) and the reaction mixture was heated under reflux for 3 hours, whereafter it was poured into ice - dilute hydrochloric acid and extracted with ether. The ethereal extract was washed with water and an aqueous solution of sodium bisulphite, dried and evaporated to dryness. There was obtained an oily residue of 4,4'-dimethoxy-α-(n-propyl)-α-hydroxy-α'-trifluoroethyl-bibenzyl.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[CH:8]([CH2:12][C:13]13[CH2:22][CH:17]4[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]4)[CH2:14]1)[CH2:20]3)[CH2:7]2.[C:23]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].C(O)CO>O>[C:23]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:10]=2[C:9](=[O:11])[CH:8]([CH2:12][C:13]24[CH2:14][CH:15]5[CH2:21][CH:19]([CH2:18][CH:17]([CH2:16]5)[CH2:22]2)[CH2:20]4)[CH2:7]3)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)c1ccc(B(O)O)cc1
Reactant: O=C1c2c(Cl)cccc2CC1CC12CC3CC(CC(C3)C1)C2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: OCCO
Solvent: O
Product: CC(C)(C)c1ccc(-c2cccc3c2C(=O)C(CC24CC5CC(CC(C5)C2)C4)C3)cc1
Temperature: 125 °C

Procedure:
71.8 g (228 mmole) 7-Chloro-2-(1-adamantylmethyl)-indan-1-one, 49 g (1.2 eq.) 4-tert-butyl-benzene boronic acid, 53 g sodium carbonate, 750 ml ethylene glycol and 150 ml water were placed in a 2 l-roundbottom flask equipped with a mechanical stirrer and a reflux condenser. The mixture was degassed three times by slight evacuation and recharging with argon. A premixed catalyst solution consisting of 103 mg (0.2 mole %) palladium acetate, 3 ml NaTPPTS (2.6 M in water, 0.8 mole %) and 2 ml of water was added and the mixture was refluxed at 125° C. until complete conversion (approx. 6 h). 300 ml of water were added and the mixture was extracted three times with 150 ml of toluene each. The combined organic layers were washed twice with 100 ml water and once with 100 ml of a saturated sodium chloride solution. Drying over magnesium sulphate and evaporation of the solvent in vacuo yielded 94.1 g (quant.) of the desired product as a yellow sticky oil. 1H-NMR (400 MHz, CDCl3): δ=7.52 (t, 1H, aromatic), 7.41, 7.36 (2×d, 4H, aromatic), 7.21 (m, 2H, aromatic), 3.37 (m, 1H, COCH), 2.77-2.68 (m, 2H, benzylic), 1.42-1.18 (m, 26H, aliphatic & C(CH3)3) ppm.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([N:14]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[NH2:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-:21][C:22]#[N:23].[Na+].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[NH2:23][C:22]([NH:15][N:14]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:9][CH:10]=1)=[O:21]
Reactant: COC(=O)CN(N)c1ccc(Oc2ccccc2)cc1
Reactant: N#C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)CN(NC(N)=O)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.6 %

Procedure:
A mixture of methyl [1-[4-phenoxyphenyl]hydrazino]acetate (Intermediate 76, 11 g, 0.004 mol), sodium cyanate (0.9 g, 0136 mol) and trifluoracetic acid (1 ml, 0.0124 mol) in dry toluene (15 ml) was stirred under nitrogen at room temperature for 1 hour. The mixture was poured into 8% sodium bicarbonate solution (75 ml) and extracted with ethyl acetate (2×75 ml). The organic extract was dried (MgSO4) and evaporated to give a pale yellow semi-solid. This was triturated with ether to give the title compound (Intermediate 77) as a white solid (0.6 g, 48%) m.p. 110°-113° C.
Reaction SMILES: [Br:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[C:4]([C:13]([OH:15])=O)[CH:3]=1.S(Cl)(Cl)=O.[NH2:20][CH2:21][C@@H:22]([OH:39])[CH2:23][N:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[CH2:26][CH2:25]1>C(N(CC)CC)C>[Br:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([C:9]([F:10])([F:11])[F:12])=[C:4]([C:13]([NH:20][CH2:21][C@@H:22]([OH:39])[CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([O:30][C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=3)[CH2:26][CH2:25]2)=[O:15])[CH:3]=1
Reactant: NC[C@@H](O)CN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1
Reactant: O=C(O)c1cc(Br)c(=O)[nH]c1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Product: O=C(NC[C@@H](O)CN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1)c1cc(Br)c(=O)[nH]c1C(F)(F)F
Yield: 46.8 %

Procedure:
Made by the method of Example 1 using 5-bromo-6-oxo-2-(trifluoromethyl)-1,6-dihydropyridine-3-carboxylic acid (0.10 g), thionyl chloride (2 mL), (2R)-1-amino-3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]propan-2-ol (0.112 g) and triethylamine (0.244 mL) to yield the title compound as a colourless solid (0.096 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=O)=[CH:4][CH:3]=1.[NH2:18][CH2:19][CH2:20][NH2:21]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[N:21][CH2:20][CH2:19][N:18]=2)=[CH:4][CH:3]=1
Reactant: O=C(C(=O)c1ccc(F)cc1)c1ccncc1
Reactant: NCCN
Solvent: ClCCl
Product: Fc1ccc(C2=NCCN=C2c2ccncc2)cc1
Temperature: 23 °C
Reaction time: 12 h

Procedure:
The compound, 1-(4-Fluorophenyl)-2-(pyridin-4-yl)ethanedione, the procedure of which may be found in U.S. Pat. No. 5,656,644, Example 13(b) whose disclosure is incorporated herein by reference in its entirety, (0.2 g, 0.87 mmol), and 1,2-diaminoethane (0.1 g, 1.67 mmol) were dissolved in methylene chloride (1 mL) and stirred under argon at 23° C. for about 12 hours. The solvent was removed in vacuo and the residue was chromatographed on silica gel eluted with 1-3% methanol in methylene chloride. Recrystallization from methylene chloride hexane gave the title compound as an yellow crystalline solid. ES (+) MS m/e=254 (MH+)
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=[C:11](Cl)[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20]([NH:27][CH2:28][CH2:29][NH2:30])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>>[C:1]([O:5][C:6]([NH:8][C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=[C:11]([NH:30][CH2:29][CH2:28][NH:27][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: COC(=O)c1ccc(Cl)nc1NC(=O)OC(C)(C)C
Product: COC(=O)c1ccc(NCCNC(=O)OC(C)(C)C)nc1NC(=O)OC(C)(C)C

Procedure:
Analogously to the preparation of Example 33A, 650 mg (2.3 mmol) of methyl 2-[(tert-butoxycarbonyl)amino]-6-chloropyridine-3-carboxylate (Example 51A) and 363 mg (2.3 mmol) of N-Boc-ethylenediamine gave 500 mg (50% of theory) of the product as a solid.
Reaction SMILES: [N:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[CH2:9][CH2:10][C:11](=[O:17])[NH:12]3)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CN(C)C.[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>CN(C=O)C>[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28]([N:4]2[CH2:5][CH2:6][N:1]([C:7]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:8]=3[CH2:9][CH2:10][C:11](=[O:17])[NH:12]4)[CH2:2][CH2:3]2)(=[O:30])=[O:29])=[CH:24][CH:23]=1
Reactant: O=C1CCc2c(cccc2N2CCNCC2)N1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)C
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N2CCN(c3cccc4c3CCC(=O)N4)CC2)cc1
Temperature: 25 °C
Yield: 48 %

Procedure:
5-(1-Piperazinyl)-3,4-dihydrocarbostyril (1.0 g) was added to a mixture of 10 ml of DMF and 0.85 ml of trimethylamine and the mixture was stirred at room temperature while slowly adding dropwise 5 ml of DMF solution containing 1.07 g of p-toluenesulfonyl chloride. After completion of addition, the reaction mixture was stirred at the same temperature as above for 30 minutes. The reaction mixture was poured into a large amount of saturated saline solution and extracted with chloroform. The extract was washed with water and dried over anhydrous sodium sulfate. Chloroform was distilled off and residual crystals were recrystallized from DMF to give 800 mg of 5-[4-(p-toluenesulfonyl)-1-piperazinyl]-3,4-dihydrocarbostyril, m.p. 302°-304° C., colorless powders.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[CH:10]=[C:9]([CH3:14])[C:8]=1[CH3:15])[CH3:2].N1C=CC=CC=1.[Br:22]Br>ClCCl>[Br:22][C:10]1[C:9]([CH3:14])=[C:8]([CH3:15])[C:7]([O:6][CH2:5][CH2:4][O:3][CH2:1][CH3:2])=[CH:12][C:11]=1[CH3:13]
Reactant: BrBr
Reactant: CCOCCOc1cc(C)cc(C)c1C
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOCCOc1cc(C)c(Br)c(C)c1C
Temperature: 0 °C
Yield: 102.4 %

Procedure:
To a mixture of 1-(2-ethoxyethoxy)-2,3,5-trimethylbenzene (1.0 g, 4.08 mmol), pyridine (0.097 mL, 1.20 mmol) and dichloromethane (10 mL) was added a solution of bromine (0.66 g, 4.12 mmol) in dichloromethane (1 mL) under stirring at 0° C., and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=49/1-hexane/ethyl acetate=4/1) to give the title compound (1.2 g, yield 99%) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([O:11][C:12]2[C:17]([C:18]([N:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH:30]4[CH2:32][CH2:31]4)[CH2:22][CH2:21]3)=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=2)[C:8]([Cl:33])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl.[CH3:66][O:67][C:68](=[O:71])[CH2:69][NH2:70].C([O-])(O)=O.[Na+]>ClCCl>[CH3:66][O:67][C:68](=[O:71])[CH2:69][NH:70][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([Cl:33])[C:9]([O:11][C:12]2[C:17]([C:18]([N:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH:30]4[CH2:31][CH2:32]4)[CH2:22][CH2:21]3)=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:10][C:2]=1[Cl:1]
Reactant: COC(=O)CN
Reactant: O=C(O)c1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)CNC(=O)c1cc(Cl)c(Oc2ncccc2C(=O)N2CCN(C3CC3)c3ccccc32)cc1Cl
Reaction time: 0.25 h
Yield: 98 %

Procedure:
To a solution of 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-benzoic acid (38 mg, 0.079 mmol, 1.0 equiv) in dichloromethane (1.5 mL) was added HATU (38.8 mg, 0.10 mmol, 1.3 equiv; [CAS RN 148893-10-1]) and triethylamine (16 mg, 22 μL, 0.16 mmol, 2.0 equiv; [CAS RN 121-44-8]). After stirring the reaction mixture for 15 min, glycine methyl ester hydrochloride (12.8 mg, 0.10 mmol, 1.3 equiv; [CAS RN 5680-79-5]) was added and stirring continued at rt for 4 h. The crude reaction product was taken up in a sat. solution of NaHCO3 (50 mL) and extracted with dichloromethane (3×40 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate to give 43 mg (99%) of the title compound as a light yellow viscous oil. MS (ISN): 555.3 [M+H]+.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][C:5]1[NH:6][C:7]2[C:12]([C:13](=[O:16])[C:14]=1[CH3:15])=[CH:11][CH:10]=[CH:9][CH:8]=2.[CH2:17]([S:23](Cl)(=[O:25])=[O:24])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>N1C=CC=CC=1.CN(C=O)C>[CH3:15][C:14]1[C:13](=[O:16])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[CH2:4][NH:3][S:23]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])(=[O:25])=[O:24]
Reactant: CCCCCCS(=O)(=O)Cl
Reactant: Cc1c(CN)[nH]c2ccccc2c1=O
Agent: Cl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CCCCCCS(=O)(=O)NCc1[nH]c2ccccc2c(=O)c1C
Temperature: 25 °C
Reaction time: 12 h
Yield: 20.5 %

Procedure:
To a solution of 2-(aminomethyl)-3-methylquinolin-4(1H)-one dihydrochloride (212 mg) in pyridine-DMF (8:1, 9 mL) was added hexanesulfonyl chloride (180 mg) under ice-cooling, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, and water (50 mL) was added to the residue, followed by extraction with ethyl acetate (100 mL). The organic layer was washed sequentially with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: chloroform/methanol=20/1) to obtain N-[(3-methyl-4-oxo-1,4-dihydroquinolin-2-yl)methyl]hexane-1-sulfonamide (56 mg).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([OH:12])=O.[CH3:13][CH:14]([CH3:38])[CH2:15][NH:16][C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:24])[CH2:20][N:19]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:18]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C>C(#N)C.C(=O)(O)[O-].[Na+]>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:16]([CH2:15][CH:14]([CH3:38])[CH3:13])[C@H:17]1[CH2:22][C@@H:21]([C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:24])[CH2:20][N:19]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:18]1)=[O:12]
Reactant: CC(C)CN[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Reactant: O=C(O)c1nc2ccccc2s1
Agent: CN(C)C(Cl)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)CN(C(=O)c1nc2ccccc2s1)[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 80.8 %

Procedure:
1,3-Benzothiazole-2-carboxylic acid (29 mg), tert-butyl(3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (50 mg) and N,N-diisopropylethylamine (118 μl) were dissolved in acetonitrile (3 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (57 mg) was added at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with 10% aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:1-1:0) was concentrated under reduced pressure to give the object product (58 mg).
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH2:9]([O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>>[Br:8][C:5]1[CH:4]=[N:3][C:2]([C:21]2[CH:22]=[CH:23][C:18]([O:17][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:19][CH:20]=2)=[N:7][CH:6]=1
Reactant: Brc1cnc(Br)nc1
Reactant: CCCCCCCCOc1ccc(B(O)O)cc1
Product: CCCCCCCCOc1ccc(-c2ncc(Br)cn2)cc1

Procedure:
2,5-Dibromopyrimidine and 4-octyloxybenzeneboronic acid are reacted analogously to Example 1 to give 5-bromo-2-(4-octyloxyphenyl) pyrimidine. ##STR34##
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:8]([OH:10])=[O:9].[CH3:20][O:21][CH2:22][CH2:23]Br.CO>CN(C=O)C>[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:8]([O:10][CH2:23][CH2:22][O:21][CH3:20])=[O:9]
Reactant: COCCBr
Reactant: O=C(O)c1cc(CO)cc(S(F)(F)(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: COCCOC(=O)c1cc(CO)cc(S(F)(F)(F)(F)F)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 57.1 %

Procedure:
At 0° C., 86 mg (2.16 mmol) of sodium hydride (60% strength suspension in mineral oil) were added to a solution of 200 mg (0.719 mmol) of the compound of Example 37A in 5.7 ml of anhydrous DMF, and the mixture was then warmed to RT. 300 mg (2.16 mmol) of 2-bromoethyl methyl ether were then added, and the reaction mixture was stirred at 60° C. for about 16 h. After cooling to RT, 1 ml of methanol was added. In two portions, the reaction mixture was then separated into its components by preparative HPLC (Method 33). The product fractions were combined and concentrated on a rotary evaporator and the residue was dried under high vacuum. This gave 58 mg (20% of theory) of the title compound. In addition, 138 mg (57% of theory) of 2-methoxyethyl 3-(hydroxymethyl)-5-(pentafluoro-λ6-sulphanyl)benzoate were isolated, which were then reacted once more in the manner described above with 2-bromoethyl methyl ether to give a further 30 mg of the title compound.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([O:12][CH:13]([CH3:19])[C:14](OCC)=[O:15])[CH2:8][CH2:9][CH2:10][CH3:11].Cl>CCOCC>[CH2:7]([O:12][CH:13]([CH3:19])[CH2:14][OH:15])[CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCOC(C)C(=O)OCC
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CCCCCOC(C)CO
Reaction time: 8 h
Yield: 86.8 %

Procedure:
7.5 g of LiAlH4 was added to 250 ml of ether, and under stirring below 10° C., 46 g of the above ester was dropped in 2 hours. After the addition, the mixture was stirred for 2 hours and left standing overnight. The mixture was acidified to pH 1 with 5%-hydrochloric acid and extracted with ether. The ether layer, after being separated, was dried with anhydrous MgSO4, followd by distilling-off of the ether to obtain 31 g of 2-pentyloxypropanol.