Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:22][OH:23])[CH2:10][CH2:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:22][O:23][S:32]([CH3:31])(=[O:34])=[O:33])[CH2:10][CH2:11][C:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)CCC(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H](CCC(=O)OCc1ccccc1)COS(C)(=O)=O

Procedure:
10.8 g (33.4 mmol) of benzyl (4R)-4-t-butoxycarbonylamino-5-hydroxypentanoate and 3.4 g (33.4 mmol) of triethylamine were stirred in 200 ml of dichloromethane. 3.83 g (33.4 mmol) of methanesulfonyl chloride was added to the obtained mixture under cooling with ice. Crude benzyl (4R)-4-t-butoxycarbonylamino-5-methanesulfonyloxypentanoate was obtained by an ordinary method with dichloromethane as the extracting solvent. The crude product was stirred together with 7.2 g (170 mmol) of lithium chloride in 50 ml of DMF at 50° C. overnight. The solvent was evaporated, and the crude title compound obtained by an ordinary method with ethyl acetate as the extracting solvent was washed with a solvent mixture of hexane and ethyl acetate to obtain the title compound.
Reaction SMILES: [CH3:1][O-:2].[Na+].CO.[Br:6][C:7]1[C:8](Cl)=[N:9][CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1>O>[Br:6][C:7]1[C:8]([O:2][CH3:1])=[N:9][CH:10]=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1
Reactant: O=[N+]([O-])c1cnc(Cl)c(Br)c1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1ncc([N+](=O)[O-])cc1Br
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium methoxide (28% methanol solution) (2 ml) was added to a methanol (2 ml) solution containing 3-bromo-2-chloro-5-nitropyridine (100 mg), followed by stirring at room temperature for 1 hour. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resultant was washed with saturated saline and dried over anhydrous sodium sulfate, the solvent was distilled away under reduced pressure, and a yellow solid of 3-bromo-2-methoxy-5-nitropyridine (96 mg) was thus obtained.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14].[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1B(O)O>>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][C:24]=3[F:26])[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[O:14]
Reactant: OB(O)c1ccc(F)cc1F
Reactant: CCCNC(=O)c1nnc2c(Br)cccc2c1N
Product: CCCNC(=O)c1nnc2c(-c3ccc(F)cc3F)cccc2c1N
Yield: 89.4 %

Procedure:
Using method A, 4-amino-8-bromo-N-propyl-cinnoline-3-carboxamide (100 mg, 0.33 mmol) and 2,4-difluorophenyl boronic acid (202 mg, 1.28 mmol) were reacted to afford the title compound (101 mg, 92.3% yield) as a pale-yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.55 (br, 1H), 7.92 (dd, J=8.0 Hz, J′=1.7 Hz, 1H), 7.70-7.80 (m, 2H), 7.49 (m, 1H), 6.90-7.05 (m, 2H), 3.46 (q, J=6.7 Hz, 2H), 1.66 (m, J=7.3 Hz, 2H), 1.00 (t, J=7.4 Hz, 3H) MS APCI, m/z=343 (M+H) HPLC 1.84 min.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:28]=[C:27]([O:29]C)[CH:26]=[CH:25][C:4]=1[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][C:16]3[CH:22]=[C:21]([O:23]C)[CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:10][CH:9]=1)=[O:6].B(Br)(Br)Br.C(Cl)Cl.CO>C(Cl)Cl>[F:32][C:2]([F:1])([F:31])[C:3]1[CH:28]=[C:27]([OH:29])[CH:26]=[CH:25][C:4]=1[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[S:15][C:16]3[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:12][CH:13]=1)=[O:6]
Reactant: COc1ccc(C(=O)Nc2ccc(-c3nc4ccc(OC)cc4s3)cc2)c(C(F)(F)F)c1
Agent: BrB(Br)Br
Solvent: CO
Solvent: ClCCl
Product: O=C(Nc1ccc(-c2nc3ccc(O)cc3s2)cc1)c1ccc(O)cc1C(F)(F)F
Reaction time: 1 h
Yield: 62.1 %

Procedure:
Prepared as described in the Demethylation section using 2-trifluoromethyl-N-[4-(6-methoxy-1,3-benzothiazol-2-yl)phenyl]-4-(methoxy)benzamide (0.30 g, 0.655 mmol) in dry DCM (15 ml) and BBr3 (1.0M in DCM, 1.4 ml, 1.4 mmol) at −78° C. under an atmosphere of argon. Stirring was continued at −78° C. for 1 h, and then the reaction mixture was allowed to rise to room temperature overnight. A further volume of BBr3 (1.0 M in DCM, 1.4 ml, 1.4 mmol) was added and the reaction mixture stirred at room temperature for 24 h to give the title compound (0.175 g, 62%) as a colourless solid after work-up and flash chromatography (15:1 DCM/MeOH).
Reaction SMILES: [NH2:1][C:2]1(C(OCC)=O)[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[C:6]2[CH:16]=[C:17]([CH2:19][CH3:20])[S:18][C:5]=2[N:4]2[C:21]([CH3:24])=[N:22][N:23]=[C:3]12>C(O)C.O>[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])[C:6]2[CH:16]=[C:17]([CH2:19][CH3:20])[S:18][C:5]=2[N:4]2[C:21]([CH3:24])=[N:22][N:23]=[C:3]12
Reactant: CCOC(=O)C1(N)N=C(c2ccccc2Cl)c2cc(CC)sc2-n2c(C)nnc21
Solvent: CCO
Solvent: O
Product: CCc1cc2c(s1)-n1c(C)nnc1C(N)N=C2c1ccccc1Cl
Temperature: 25 °C
Reaction time: 24 h
Yield: 85.1 %

Procedure:
In a mixture of 180 ml of ethanol and 60 ml of water was dissolved 15.1 g of ethyl 6-amino-4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-carboxylate. To the solution was added 6.0 g of crystals of barium hydroxide·8 hydrate, and the mixture was stirred at room temperature for 24 hours. After the solvent was distilled off under reduced pressure, 200 ml of water and 100 ml of benzene were added and the mixture was stirred fully. The water layer was separated, adjusted to pH 2 with 1N hydrochloric acid and left standing still for 24 hours. Thereafter, the mixture was neutralized with sodium carbonate, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in chloroform and insoluble matters were filtered off. After the solvent was distilled off under reduced pressure, the residue was recrystallized from ethanol to give 10.7 g of 6-amino-4-( 2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]-diazepine, m.p. 130°-131° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH:7]=[CH:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13]O)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.Br.COC1C=CC(CC2C=CC(C[Br:32])=CC=2)=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH:7]=[CH:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13][Br:32])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(Cc2ccc(CBr)cc2)cc1
Reactant: COc1ccc(C=Cc2ccc(CO)cc2)cc1
Agent: Br
Solvent: ClCCl
Product: COc1ccc(C=Cc2ccc(CBr)cc2)cc1

Procedure:
4-(4-Methoxystyryl)benzyl bromide was prepared from 55 g. of 4-(4-methoxystyryl)benzyl alcohol and hydrogen bromide in 750 ml. of methylene dichloride according to the procedure of Example 1, part (e); yield 50 g., m.p. 147°-148° C. when recrystallized from ethyl acetate.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[O:13][CH3:14].[CH3:15][O:16][CH2:17][CH2:18]Br.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:14][O:13][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=1[O:1][CH2:18][CH2:17][O:16][CH3:15])[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: CCOC(=O)c1ccc(O)c(OC)c1
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)c1ccc(OCCOC)c(OC)c1
Yield: 10.2 %

Procedure:
A mixture of ethyl 4-hydroxy-3-methoxybenzoate (9.8 g, 50 mmol), 2-bromoethyl methyl ether (8.46 ml, 90 mmol) and potassium carbonate (12.42 g, 90 mmol) in acetone (60 ml) was heated at reflux for 30 hours. The mixture was allowed to cool and the solids removed by filtration. The volatiles were removed from the filtrate by evaporation and the residue triturated with hexane to give ethyl 3-methoxy-4-(2-methoxyethoxy)benzoate ( 1.3 g, 89%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11]1[N:16]=[CH:15][C:14]([CH2:17][C:18]([NH2:20])=[O:19])=[C:13]([NH:21][CH2:22][C:23]2[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=2)[CH:12]=1.N[C:32]1C=CC(C#N)=CC=1NC1N=CC(CC(N)=O)=C(NCC2C=C(F)C=C(F)C=2)C=1.C(OC)(OC)OC>>[C:8]([C:6]1[CH:5]=[CH:4][C:3]2[N:10]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][C:18]([NH2:20])=[O:19])=[C:13]([NH:21][CH2:22][C:23]4[CH:24]=[C:25]([F:30])[CH:26]=[C:27]([F:29])[CH:28]=4)[CH:12]=3)[CH:32]=[N:1][C:2]=2[CH:7]=1)#[N:9]
Reactant: N#Cc1ccc(N)c(Nc2cc(NCc3cc(F)cc(F)c3)c(CC(N)=O)cn2)c1
Reactant: N#Cc1ccc(Nc2cc(NCc3cc(F)cc(F)c3)c(CC(N)=O)cn2)c(N)c1
Solvent: COC(OC)OC
Product: N#Cc1ccc2c(c1)ncn2-c1cc(NCc2cc(F)cc(F)c2)c(CC(N)=O)cn1

Procedure:
From the mixture of 6-[(2-amino-4-cyanophenyl)amino]-4-[(3,5-difluorobenzyl)amino]pyridine-3-carboxyamide and 6-[(2-amino-5-cyanophenyl)amino]-4-[(3,5-difluorobenzyl) amino]pyridine-3-carboxyamide (1H-NMR integral ratio 3:1) and trimethyl orthoformate in a manner similar to step 2 of Example 365, the title compound was obtained as a white solid (yield 45%).
Reaction SMILES: [F:1][C:2]1([F:34])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([O:30]C)=[CH:27][C:28]=5[CH3:29])[C:20]([CH3:32])=[C:19]([CH3:33])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[Si](I)(C)(C)C.CO>CC#N>[F:34][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([OH:30])=[CH:27][C:28]=5[CH3:29])[C:20]([CH3:32])=[C:19]([CH3:33])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1
Reactant: COc1cc(C)c(-c2nc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)cc(C)c2C)cn1
Agent: C[Si](C)(C)I
Solvent: CC#N
Solvent: CO
Product: Cc1cc(O)ncc1-c1nc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)cc(C)c1C
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 49 %

Procedure:
To a suspension of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-3,4,4′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (17 mg, 0.036 mmol) in CH3CN (0.7 mL) was added TMSI (10 uL, 0.072 mmol) dropwise at 20° C. The reaction was stirred at 50° C. for 30 min. Additional TMSI (10 uL, 0.072 mmol) was added and the reaction was heated at 50° C. for 2 h. Additional TMSI (10 uL, 0.072 mmol) was added and the reaction was heated at 70° C. for 2 h. MeOH (1.0 mL) was added and the solution was re-partitioned between EtOAc and H2O. The organic layer was washed with NaHSO3 (2×), brine, dried over MgSO4 and evaporated to dryness to yield a white solid that was further purified by preparative TLC (10% MeOH-EtOAc) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-hydroxy-3,4,4′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (8 mg, 49%). 1H NMR (400 MHz, MeOD) 7.92 (s, 1H), 7.28 (d, J=1.6 Hz, 1H), 7.22 (dd, J=1.7, 8.3 Hz, 1H), 7.14-7.10 (m, 2H), 6.36 (s, 1H), 2.27 (s, 3H), 1.95 (s, 3H), 1.81 (d, J=0.6 Hz, 3H), 1.56 (dd, J=3.9, 7.0 Hz, 2H), 1.14 (dd, J=3.9, 7.0 Hz, 2H). Retention time: 1.49 min; ESI-MS m/z calc. 453.4. found 454.2 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1)#[N:2]
Reactant: CCCCCCCCCCBr
Reactant: N#Cc1ccc(-c2ccc(O)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CCCCCCCCCCOc1ccc(-c2ccc(C#N)cc2)cc1

Procedure:
A mixture of 4-cyano-4'-hydroxybiphenyl (56) (10.10 g, 0.052 mol), 1-bromodecane (14.38 g, 0.065 mol), anhydrous potassium carbonate (37.32 g, 0.27 mol), butanone (300 ml) and a trace of potassium iodide was heated under reflux overnight. The cooled solution was filtered to remove inorganic salts and the solvent was removed in vacuo. The residual oil was distilled (to remove excess bromide) and finally purified by column chromatography (dichloromethane) to yield a colourless, low melting solid.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([N+:12]([O-])=O)[CH:8]=[CH:7][CH:6]=2.[H][H]>CO.O=[Pt]=O>[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([NH2:12])[C:10]=2[CH:11]=1
Reactant: Cc1cc2c([N+](=O)[O-])cccc2cn1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CO
Product: Cc1cc2c(N)cccc2cn1
Yield: 45 %

Procedure:
3-Methyl-5-nitroisoquinoline (Description 44; 660 mg, 3.51 mmol) was dissolved in MeOH (30 ml) and PtO2 catalyst (120 mg) was added. The mixture was stirred for 1 hour 45 minutes under a balloon of hydrogen, then the catalyst was filtered off, washing with more methanol. The filtrate was evaporated and purified by flash column chromatography using as eluant 5% methanol in dichloromethane to give the title compound (250 mg).
Reaction SMILES: [CH:1]1([CH2:4][N:5]([CH2:18][CH2:19][CH2:20][OH:21])[C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:7]=2)[CH2:3][CH2:2]1.[F:22][C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][CH:24]=1>>[CH:1]1([CH2:4][N:5]([CH2:18][CH2:19][CH2:20][O:21][C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:16])([F:17])[F:15])[CH:7]=2)[CH2:2][CH2:3]1
Reactant: Oc1ccc(F)cc1
Reactant: N#Cc1ccc(N(CCCO)CC2CC2)cc1C(F)(F)F
Product: N#Cc1ccc(N(CCCOc2ccc(F)cc2)CC2CC2)cc1C(F)(F)F

Procedure:
Synthesized as described in Example 1C from 4-[(cyclopropylmethyl)(3-hydroxypropyl)amino]-2-(trifluoromethyl)benzonitrile and 4-fluorophenol: MS (APCI) m/z 393 (M+1).
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C@H:14]([CH2:36][CH3:37])[C:15]([NH:17][C:18]1[CH:19]=[N:20][C:21]([O:24][C:25]2[C:33]3[CH:32]([CH2:34][CH3:35])[O:31][CH2:30][C:29]=3[CH:28]=[CH:27][CH:26]=2)=[CH:22][CH:23]=1)=[O:16]>ClCCl>[CH2:36]([C@H:14]1[NH:13][C:2](=[O:4])[N:17]([C:18]2[CH:19]=[N:20][C:21]([O:24][C:25]3[C:33]4[CH:32]([CH2:34][CH3:35])[O:31][CH2:30][C:29]=4[CH:28]=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)[C:15]1=[O:16])[CH3:37]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CCC1OCc2cccc(Oc3ccc(NC(=O)[C@H](N)CC)cn3)c21
Solvent: ClCCl
Product: CCC1OCc2cccc(Oc3ccc(N4C(=O)N[C@H](CC)C4=O)cn3)c21
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 71.2 %

Procedure:
In a 50 ml round-bottomed flask (2R)-2-amino-N-{6-[(3-ethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}butanamide (Intermediate 110, 9 mg) was dissolved in dichloromethane (2 ml) to give a pale yellow solution that was cooled at 0° C. TEA (0.017 ml, 0.119 mmol) was added. 0.5 ml of a solution of triphosgene (14 mg in 2 ml of dichloromethane) was added dropwise to the reaction mixture at 0° C. The reaction mixture was stirred at 0° C. After 20 minutes, the reaction was completed. The reaction mixture was evaporated under vacuum to afford the crude product as a pale yellow oil which was purified via Biotage SP1 (with Cyclohexane/EtOAc as eluents from 2:1 to 1:2 in 15 CV; then 1:2 for 10 CV; 10 g SNAP Silica column). The collected fractions afforded the title compound (5R)-5-ethyl-3-{6-[(3-ethyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-3-pyridinyl}-2,4-imidazolidinedione (6.9 mg) as a white solid.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[S:14][C:13](Cl)=[C:12](Cl)[C:10]1=[O:11]>C1(C)C(C)=CC=CC=1>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[S:14][CH:13]=[CH:12][C:10]1=[O:11]
Reactant: CCCCCCCCn1sc(Cl)c(Cl)c1=O
Solvent: Cc1ccccc1C
Product: CCCCCCCCn1sccc1=O

Procedure:
The core material is prepared as a mixture of 100 grams of Kathon 287T (97%) manufactured by Rohm and Haas and 100 grams of a substituted aromatic solvent, SAS 310 manufactured by Nisseki Chemical and heated to 40° C. The aqueous phase and the core material are added to a 1-quart Waring Blender jar and the slurry is emulsified at moderate speed for about 15 minutes to produce an oil-in-water emulsion of droplets in the size range of about 10 to 40 microns. The emulsion is transferred to a 1-liter beaker. The slurry is slowly agitated using a turbine impellor while maintaining the temperature at about 40° C. A solution of 4 grams of urea and 10 grams of resorcinol in 60 grams of water is slowly added to the emulsion. A solution of 2 grams sodium sulfate in 30 grams of water is subsequently added to the slurry in drop-wise fashion. A 30 ml 37% formaldehyde solution is added drop-wise followed 10 minutes later by the addition of 20 ml of a 10% sulfuric acid solution over a 5-minute period. The slurry is warmed to 45° C. and after about one hour a solution of 4 g of urea, 6 g of resorcinol, 50 g of water and 20 ml of 37% formaldehyde second addition is added drop-wise. This solution may be divided, with half added in 15 minutes followed by a 15-minute hold period prior to adding the second half. One hour later another solution like the proceeding is added to the slurry in the same fashion. The slurry is heated to 55° C. and allowed to stir for 16 hours. The microcapsule slurry is cooled to ambient temperature and pH adjusted to 7.0 using 10% sodium hydroxide solution. The slurry is then diluted with water and strained using a 125-150 um sieve to remove encapsulated air and any debris. The slurry is set aside to allow the microcapsules to settle. The supernatant liquid is decanted and microcapsule concentrate is re-slurried with water. A small amount of Syloid 244 silica from W. R. Grace Company is stirred into the slurry; and the microcapsules are vacuum-filtered using Whatman 4.0 paper and tray dried to produce 230 grams of dry free-flowing powder. The resultant microcapsules are mostly 10-40 microns and can be incorporated in a marine coating composition to impart anti-fouling properties. The microcapsules were tested for stability in xylene by placing a 50-mg sample into 50 mls of xylene and periodically analyzing a small aliquot of the xylene spectrophotometrically for the presence of DCOIT to determine the amount diffused through the capsule shell. Samples were tested after room storage. 1.1% DCOIT was released after 56 days at room temperature.
Reaction SMILES: [C@@H:1]1([OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][C@@H:2]1[OH:7].F[C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[N+:17]([O-:19])=[O:18]>>[F:16][C:14]1[CH:13]=[CH:12][C:11]([N+:17]([O-:19])=[O:18])=[C:10]([CH:15]=1)[O:7][C@H:2]1[CH2:3][CH2:4][CH2:5][CH2:6][C@H:1]1[OH:8]
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: O[C@@H]1CCCC[C@@H]1O
Product: O=[N+]([O-])c1ccc(F)cc1O[C@H]1CCCC[C@H]1O

Procedure:
Prepared analogously to III.1 from cis-1,2-cyclohexandiol (1.0 g) and 0.94 ml 2,4-difluoronitrobenzene.
Reaction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
Reactant: C=CCCCCSc1nc(N)c2ncn([C@@H]3O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](O)[C@H]3O)c2n1
Reactant: C=CCCCCSc1nc(N)c2ncn([C@@H]3O[C@H](COP(=O)([O-])OP(=O)([O-])OP(=O)([O-])[O-])[C@@H](O)[C@H]3O)c2n1
Agent: [NH4+]
Product: C=CCCCCSc1nc(N)c2ncn([C@@H]3O[C@H](COP(=O)([O-])OP(=O)([O-])[O-])[C@@H](O)[C@H]3O)c2n1

Procedure:
NMR of 2-(5-hexenylthio)adenosine 5'-triphosphate tetraammonium salt: 1H NMR (D2) d: 8.41 (S, 1H, H-8), 6.13 (d, J=5.7 Hz, 1H, H-1'), 4.64 (m, 1H, H-3'), 4.37 (m, 1H, H-4'), 4.24 (din, 2H, H-5'). High Res. FAB: calcd. for C16H25O13N5P3S: 620.0382. Found: 620.0428. Retention time: 7.7 min (91% purity) using solvent system I, 7.4 min (>98% purity) using solvent system II. 2-(5-Hexenylthio)adenosine 5'-triphosphate was also synthesized by the triphosphorylation procedure recited in Example 1.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[NH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1>O1CCOCC1.O>[F:24][CH:23]([F:25])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([NH:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=1
Reactant: NCc1ccccn1
Reactant: FC(F)c1nc2ccccc2n1-c1nc(Cl)nc(N2CCOCC2)n1
Solvent: C1COCCO1
Solvent: O
Product: FC(F)c1nc2ccccc2n1-c1nc(NCc2ccccn2)nc(N2CCOCC2)n1
Yield: 50.2 %

Procedure:
A stirred mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (0.183 g, 0.5 mmol) and 2-aminomethylpyridine (0.135 g, 1.25 mmol) in 10 mL dioxane was heated gently until a clear solution was obtained. After cooling, the mixture was diluted with water to give an oily solid, which was recrystallized from aqueous MeOH to give 0.11 g (50% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyridinylmethyl)-1,3,5-triazin-2-amine: mp 192-193° C.; 1H NMR (CDCl3) (rotamers) δ8.65 (d, J=1.8 Hz, 1H), 8.57 (dd, J=4.7, 1.0 Hz, 1H), 8.40 and 8.25 (2d, J=7.5 and 5.5 Hz, 1H), 7.88 (m, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.62 (t, JHF=54.5 Hz, 1H), 7.43-7.37 (m, 2H), 7.30 (ddd, J=7.9, 4.8, 0.7 Hz, 1H), 5.75 and 5.64 (2 m, exchangeable with D2O, 1H), 4.76 and 4.69 (2 d, J=5.7 and 5.8 Hz, 2H), 3.87 (m, 4H), 3.78 (m, 4H); Anal. Calcd. for C21H20F2N8O: C, 57.5; H, 4.6; N, 25.6. Found: C, 57.5; H, 4.5; N, 25.6%.