Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H][H].[F:3][C:4]([F:15])=[C:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[CH3:6]>C(O)(=O)C.[Pd]>[F:3][CH:4]([F:15])[CH:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[CH3:6]
Reactant: COc1ccc(C(C)=C(F)F)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(=O)O
Product: COc1ccc(C(C)C(F)F)cc1

Procedure:
At 50° C. and 1 atm hydrogen pressure, 24.2 g of 1-(2,2-difluoro-1-methylvinyl)-4-methoxybenzene in 300 ml of glacial acetic acid were hydrogenated using palladium on carbon as catalyst until no further hydrogen uptake was visible. The catalyst was filtered off and the reaction solution was concentrated, to give the title product as a colourless oil which was reacted further without any purification.
Reaction SMILES: [C:1]1(C)[CH:6]=CC(S(OCC=C)(=O)=O)=C[CH:2]=1.[CH3:15][C:16]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:17]=1[NH2:18]>O>[CH3:15][C:16]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:17]=1[NH:18][CH2:6][CH:1]=[CH2:2]
Reactant: Cc1cccc(C)c1N
Reactant: C=CCOS(=O)(=O)c1ccc(C)cc1
Solvent: O
Product: C=CCNc1c(C)cccc1C

Procedure:
Allyl p-toluenesulphonate (10.6 g, 0.05 mole) was heated with 2,6-dimethylaniline (6.0 g, 0.05 mole) in a steam bath for 2 hours, poured into water (100 ml), extracted into methylenedichloride (50 ml), dried (MgSO4), filtered, solvent evaporated and the product distilled to give 2,6-dimethylphenyl allylamine, identical with that in Route II. Subsequent steps were the same as for Route II.
Reaction SMILES: C(NC(C)C)(C)C.C([Mg]Br)C.[C:12]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[CH3:13].[CH2:20]([O:27][C:28]1[CH:29]=[C:30]([C:34]#[N:35])[CH:31]=[N:32][CH:33]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>C(OCC)C>[NH2:35][C:34]([C:30]1[CH:31]=[N:32][CH:33]=[C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:29]=1)=[CH:13][C:12]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]
Reactant: N#Cc1cncc(OCc2ccccc2)c1
Reactant: CC(=O)OC(C)(C)C
Agent: CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: CC(C)NC(C)C
Product: CC(C)(C)OC(=O)C=C(N)c1cncc(OCc2ccccc2)c1
Reaction time: 0.5 h

Procedure:
Diisopropylamine (12.8 mL, 91 mmol) was added at 0° C. to a 3M solution of ethyl magnesium bromide in diethyl ether (15 mL, 45 mmol) and additional diethyl ether (40 mL). After one hour at 0° C. t-butyl acetate was added and stirring was continued for 30 minutes. 5-(benzyloxy)pyridine-3-carbonitrile (2.9 g, 13.8 mmol) in diethyl ether (40 mL) was added at 0° C. After 2.5 hours at 0° C. saturated aqueous ammonium chloride solution was added. Phases were separated and the aqueous phase was extracted with diethyl ether. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane, 0 to 45%) to yield 1.95 g tert-butyl 3-amino-3-[5-(benzyloxy)pyridin-3-yl]prop-2-enoate.
Reaction SMILES: C(O[BH-](O[C:11](=O)[CH3:12])OC(=O)C)(=O)C.[Na+].[NH2:15][CH:16]([CH2:24][NH:25][C:26]1[C:31]([CH2:32][CH3:33])=[C:30]([N:34]2[CH2:39][CH2:38][CH:37]([C:40]3[CH:49]=[CH:48][C:47]4[CH2:46][CH2:45][CH2:44][NH:43][C:42]=4[N:41]=3)[CH2:36][CH2:35]2)[N:29]=[CH:28][N:27]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>O1CCCC1>[CH2:31]([CH:32]([CH2:11][CH3:12])[CH2:33][NH:15][CH:16]([CH2:24][NH:25][C:26]1[C:31]([CH2:32][CH3:33])=[C:30]([N:34]2[CH2:35][CH2:36][CH:37]([C:40]3[CH:49]=[CH:48][C:47]4[CH2:46][CH2:45][CH2:44][NH:43][C:42]=4[N:41]=3)[CH2:38][CH2:39]2)[N:29]=[CH:28][N:27]=1)[C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH3:30]
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: CCc1c(NCC(N)C(=O)OC(C)(C)C)ncnc1N1CCC(c2ccc3c(n2)NCCC3)CC1
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1c(NCC(NCC(CC)CC)C(=O)OC(C)(C)C)ncnc1N1CCC(c2ccc3c(n2)NCCC3)CC1
Reaction time: 0.17 h

Procedure:
75 mg (0.35 mmoles) of sodium triacetoxyborohydride in 6 ml of tetrahydrofuran is left under stirring for 10 minutes at TA. Then a mixture of 100 mg (0.208 mmoles) of tert-butyl 2-amino-3-{5-ethyl-6-[4-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-piperidin-1-yl]pyrimidin-4-ylamino}-propionate and 0.228 mmoles of 2-ethyl-butylaldehyde in solution in 3 ml of tetrahydrofuran is added. The reaction mixture is stirred at ambient temperature for 4 hours 30 minutes. Then it is extracted with ethyl acetate after washing with a saturated solution of sodium bicarbonate. The organic phase obtained is dried over magnesium sulphate before being concentrated to dryness under reduced pressure (2 kPa). The residue is then chromatographed on silica gel with the following eluent: ethyl acetate-dichloromethane/methanol (80/20) 50-50. A mass my of expected product is obtained.
Reaction SMILES: [OH-].[Li+].[Br:3][C:4]1[N:5]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]([CH:30]3[CH2:32][CH2:31]3)=[CH:22][CH:21]=2)[C:6]([S:9][CH2:10][C:11]([NH:13][CH2:14][C:15]([O:17]CC)=[O:16])=[O:12])=[N:7][N:8]=1>C1COCC1.O>[Br:3][C:4]1[N:5]([C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]([CH:30]3[CH2:32][CH2:31]3)=[CH:22][CH:21]=2)[C:6]([S:9][CH2:10][C:11]([NH:13][CH2:14][C:15]([OH:17])=[O:16])=[O:12])=[N:7][N:8]=1
Reactant: CCOC(=O)CNC(=O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CNC(=O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Aqueous lithium hydroxide solution (1M, 0.8 mL, 0.8 mmol) is added to a solution of ethyl 2-(2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetamido)acetate (0.4 mmol) in 3:1, THF/H2O (1.6 mL) and the mixture stirred for 18 h at room temperature. The crude reaction mixture is concentrated and acidified with aqueous HCl (1M, 1.2 mL) and then is extracted with ethyl acetate (3×3 mL). The combined organic extracts are dried (sodium sulfate), filtered and concentrated to provide 2-(2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetamido)acetic acid.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[C:13]([OH:15])=[O:14].OS(O)(=O)=O.[CH3:21]O>>[OH:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]=1[C:13]([O:15][CH3:21])=[O:14]
Reactant: O=C(O)c1[nH]c2ccccc2c1CCO
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1[nH]c2ccccc2c1CCO

Procedure:
To a solution of 3-(2-hydroxyethyl)-1H-indole-2-carboxylic acid (5.589 g, 26.1 mmol) in methanol (75 mL) was added concentrated H2SO4 (3 mL), and the mixture was refluxed overnight. The solvent was removed under a reduced pressure and the residual oil was dissolved in EtOAc. The organic solution was washed with a saturated aqueous NaHCO3 solution, dried over Na2SO4, and concentrated to give 5.670 g of methyl 3-(2-hydroxyethyl)-1H-indole-2-carboxylate as an oil. This material was used for the next reaction without further purification: 1H NMR (CDCl3) δ 2.21 (brs, 1H), 3.40 (t, J=6.5 Hz, 2H), 3.88 (s, 3H), 3.94 (t, J=6.5 Hz, 2H), 7.14 (ddd, J=1.7, 6.3, and 8.1 Hz, 1H), 7.2–7.4 (m, 2H), 7.70 (d, J=8.1 Hz, 1H), 9.07 (brs, 1H).
Reaction SMILES: [C:1]1([S:7]([N:10]2[CH2:17][CH:16]3[NH:18][CH:12]([CH2:13][O:14][CH2:15]3)[CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[BH3-][C:22]#N.[Na+]>CC#N.CC(O)=O>[CH3:22][N:18]1[CH:12]2[CH2:13][O:14][CH2:15][CH:16]1[CH2:17][N:10]([S:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)(=[O:9])=[O:8])[CH2:11]2
Reactant: [BH3-]C#N
Reactant: O=S(=O)(c1ccccc1)N1CC2COCC(C1)N2
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC#N
Product: CN1C2COCC1CN(S(=O)(=O)c1ccccc1)C2
Reaction time: 2 h
Yield: 70.8 %

Procedure:
To a solution of 112f (2.0g, 7.5 mmol) in MeCN (60 ml) was added HCHO (1.4 ml, 16 mmol) and 5 drops of AcOH at room temperature. Then NaCNBH3 (1 g, 16 mmol) added and the mixture was stirred for 2h. It was poured onto water and extracted with EA (100*3). The organic layer was dried over Na2SO4, filtered off, evaporated, and purified through a silica gel column eluting with PE:EA=5:1 to 1:1 to give 112g as a colorless oil (1.5g, 72%) MS: [M+H]+: 283
Reaction SMILES: O1CCO[CH:2]1[CH2:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)=O.[C:18]([NH:21][CH2:22][CH2:23][NH2:24])(=[O:20])[CH3:19]>C(O)(=O)C>[CH3:17][O:16][C:13]1[CH:12]=[CH:11][C:10]([C:8]2[N:24]([CH2:23][CH2:22][NH:21][C:18](=[O:20])[CH3:19])[CH:2]=[CH:6][CH:7]=2)=[CH:15][CH:14]=1
Reactant: COc1ccc(C(=O)CCC2OCCO2)cc1
Reactant: CC(=O)NCCN
Solvent: CC(=O)O
Product: COc1ccc(-c2cccn2CCNC(C)=O)cc1
Yield: 65.5 %

Procedure:
3-(1,3-Dioxolan-2-yl)-4'-methoxypropiophenone (38.8 g) was dissolved in 100 ml of acetic acid and added under argon and while stirring to a solution of 33.5 g of N-acetylethylene-diamine in 500 ml of acetic acid. The reaction solution was heated to reflux overnight, the acetic acid was subsequently removed in a vacuum. The residue was taken up in 500 ml of methylene chloride and washed with a mixture of 200 ml of saturated sodium hydrogen carbonate solution and 400 ml of 2N sodium hydroxide solution. The aqueous phase was extracted three times with 100 ml of methylene chloride each time, the organic phases were combined, dried with MgSO4 and freed from solvent. The residue, 49.6 g of brown oil, was chromatographed on 500 g of silica gel with ethyl acetate as the eluent. 27.8 g (66%) of N-[2-[2-(p-methoxyphenyl)-pyrrol-1-yl]ethyl]acetamide were isolated as a yellow-brown oil. MS: m/e=258 (M+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.Cl[Si:10]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:11][CH2:12][CH2:13][CH3:14]>>[Br:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Si:10]([CH2:15][CH2:16][CH2:17][CH3:18])([CH2:19][CH2:20][CH2:21][CH3:22])[CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]=1
Reactant: Brc1cccc(Br)c1
Reactant: CCCC[Si](Cl)(CCCC)CCCC
Product: CCCC[Si](CCCC)(CCCC)c1cccc(Br)c1

Procedure:
1-Bromo-3-tri-n-butylsilanyl-benzene is prepared in a manner analogous to the procedure described in examples 1 and 1a utilizing 1,3-dibromobenzene and chloro-tri-n-butylsilane as the ClSiR1R2R3 compound.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.[Mg].II.Br[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1>C(OCC)C>[S:3]1[CH:4]=[CH:5][CH:6]=[C:2]1[C:19]1[C:20]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]=[CH:17][CH:18]=1
Reactant: Brc1cccc2ccccc12
Reactant: Brc1cccs1
Agent: II
Agent: [Mg]
Solvent: CCOCC
Product: c1csc(-c2cccc3ccccc23)c1
Reaction time: 0.5 h

Procedure:
2-Bromothiophene(1.45 ml, 0.015 m) in diethyl ether (20 ml) was added slowly to magnesium turnings (0.48 g, 0.02 m) and iodine (trace) in diethyl ether (10 ml). It was stirred for 30 min before being added to 1-bromonaphthalene (2.07 g, 0.01 m) and catalyst in diethyl ether (25 ml). The reaction was worked up the usual way yielding a brown oil (2.49 g). The brown oil was purified by column chromatography. Flash silica (104 g) eluted with petroleum ether (600 ml) and increased to 5% diethyl diethyl ether/petroleum ether separated a clear pale green oil (1.50 g, 71% yield); m/z 210 (M+); (Found: C, 80.26; H, 4.91; S, 15.10. C14H10S requires: C, 80.00; H, 4.76; S, 15.24); H NMR (CDCl3), δ7.17 (dd, J=3.2, 5.6 Hz 1H), δ7.23 (dd, J=<1, 3.2 Hz, 1H), δ7.41 (dd, J=<1, 5.6 Hz, 1H), δ7.45 (d, J=4.8 Hz, 1H), δ7.47 (d, J=4.8 Hz, 1H) δ7.48 (d, J=8 Hz, 1H), δ7.55 (dd, J=<1, 8 Hz, 1H), δ7.83 (d, J=8 Hz, 1H), δ 7.88 (dd J=3.2, 4.8 Hz, 1H), δ8.20 (dd, J=5.6, 4.8 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[N:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[C:20](OC(=O)C)(=[O:22])[CH3:21].C(N(CC)CC)C>CN(C1C=CN=CC=1)C>[C:20]([NH:1][C:2]1[N:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1)(=[O:22])[CH3:21]
Reactant: Nc1cc2ncnc(Nc3cccc(Br)c3)c2cn1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Product: CC(=O)Nc1cc2ncnc(Nc3cccc(Br)c3)c2cn1
Yield: 7.7 %

Procedure:
A mixture of 7-amino-4-(3-bromoanilino)-pyrido[4,3-d]pyrimidine (0.154 g, 0.49 mmol), acetic anhydride (0.14 mL, 1.5 mmol), triethylamine (0.14 mL, 1.0 mmol) and a catalytic amount of 4-(N,N-dimethyl-amino)pyridine are stirred under N2 at room temperature for 18 h. The reaction is then quenched by addition of ice water. The dark precipitate is collected by Buchner filtration and is purified by preparative tlc (Rf=0.25, 7% MeOH/CHCl3). Recrystallization from EtOH gives 7-acetylamino-4-(3-bromoanilino)pyrido[4,3-d]-pyrimidine (13.5 mg, 7.7%). 1H NMR (DMSO) δ 10.92 (1H, s), 10.22 (1H, s), 9.64, (1H, s), 8.70 (1H, s), 8.28 (1H, s), 8.21 (1H, s), 7.88 (1H, d, J=7.7Hz) 7.41-7.34 (3H, m), 2.16 (3H, s).
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[C:5]([C:10]2[CH:15]=[CH:14][C:13](=[O:16])[NH:12][CH:11]=2)=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[N:3]=1.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CN(C)C=O>[NH2:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[C:5]([C:10]2[CH:15]=[CH:14][C:13](=[O:16])[N:12]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:11]=2)=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[N:3]=1
Reactant: Cn1c(N)nc(-c2cccc(F)c2)c(-c2ccc(=O)[nH]c2)c1=O
Reactant: OB(O)c1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: Cn1c(N)nc(-c2cccc(F)c2)c(-c2ccc(=O)n(-c3ccccc3)c2)c1=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 31.7 %

Procedure:
In a flask were placed 2-amino-6-(3-fluorophenyl)-3-methyl-5-(6-oxo-1,6-dihydro-3-pyridinyl)-3,4-dihydro-4-pyrimidinone (40 mg, 0.13 mmol), copper acetate (3 mg, 0.01 mmol), phenylboronic acid (31 mg, 0.26 mmol), pyridine (21 μL, 0.26 mmol) and N,N-dimethylformamide (2 mL), followed by stirring at room temperature for 24 hour. After filtering off the insoluble matters, the filtrate was purified by HPLC, to give the title compound (16 mg). MS m/e (ESI) 389 (MH+).
Reaction SMILES: [NH2:1][C@@H:2]([C:6]([OH:8])=[O:7])[C@H:3]([CH3:5])[OH:4].C([O-])(O)=O.[Na+].[CH2:14]([O:20][C:21](N1C=CC=CC1=O)=[O:22])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>O.C1COCC1>[OH:4][C@@H:3]([CH3:5])[C@@H:2]([NH:1][C:21]([O:20][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:22])[C:6]([OH:8])=[O:7]
Reactant: C[C@H](O)[C@@H](N)C(=O)O
Reactant: CCCCCCOC(=O)n1ccccc1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCOC(=O)N[C@@H](C(=O)O)[C@H](C)O
Reaction time: 15 h
Yield: 87.3 %

Procedure:
To a stirred mixture of D-threonine (0.150 g, 1.25 mmol) and NaHCO3 (0.158 g, 1.89 mmol) in H2O (3.5 mL), the crude mixture containing hexyl-2-pyridyl-carbonate and hexyl-2-oxopyridine-1-carboxylate (0.45 g, 1.89 mmol) in THF (3.5 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×5 mL). The aqueous phase was acidified with 2.0 M HCl solution to pH 2-3 and subsequently extracted with EtOAc (3×10 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.27 g, 88%) as transparent oil, which was used in the next step without further purification. 1H NMR (DMSO-d6) δ 0.83-0.90 (m, 3H), 1.08 (d, J=6.3 Hz, 3H), 1.21-1.36 (m, 6H), 1.49-1.59 (m, 2H), 3.89-3.99 (m, 3H), 4.01-4.11 (m, 1H), 6.67 (d, J=9.0 Hz, 1H), 12.30 (br s, 1H).
Reaction SMILES: [CH:1]([NH:4][S:5]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1)(=[O:7])=[O:6])([CH3:3])[CH3:2].[CH2:17]([O:19][C:20]([C:22]1[C:23](=[O:42])[C:24]2[CH:29]=[N:28][C:27](S(C)(=O)=O)=[N:26][C:25]=2[N:34]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH:35]=1)=[O:21])[CH3:18]>>[CH2:17]([O:19][C:20]([C:22]1[C:23](=[O:42])[C:24]2[CH:29]=[N:28][C:27]([NH:16][C:13]3[CH:12]=[CH:11][C:10]([CH2:9][CH2:8][S:5](=[O:7])(=[O:6])[NH:4][CH:1]([CH3:3])[CH3:2])=[CH:15][CH:14]=3)=[N:26][C:25]=2[N:34]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH:35]=1)=[O:21])[CH3:18]
Reactant: CCOC(=O)c1cn(C2CCCCC2)c2nc(S(C)(=O)=O)ncc2c1=O
Reactant: CC(C)NS(=O)(=O)CCc1ccc(N)cc1
Product: CCOC(=O)c1cn(C2CCCCC2)c2nc(Nc3ccc(CCS(=O)(=O)NC(C)C)cc3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 1(g) the title compound was prepared from 2-(4-amino-phenyl)-ethanesulfonic acid isopropylamide (from Example 33(B), 68 mg, 0.28 mmol) and 8-cyclohexyl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (from Example 17(e), 100 mg, 0.26 mmol). The title compound was obtained as a yellow solid (50 mg, 35%). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.34 (s, 1H), 8.54 (s, 1H), 7.88 (br, 1H), 7.61 (d, J=8.3 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 5.10 (m, 1H), 4.40 (q, J=7.1 Hz, 2H), 4.17 (m, 1H), 3.66 (m, 1H), 3.29 (m, 2H), 3.14 (m, 2H), 2.06 (m, 4H), 1.86 (m, 1H), 1.68 (m, 2H), 1.51 (m, 2H), 1.41 (t, J=7.1 Hz, 3H), 1.31(m, 1H), 1.24 (s, 3H), 1.23 (s, 3H).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[OH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][CH2:11][Cl:12])=[CH:8][CH:7]=1.O>C(O)(=O)C>[OH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][CH2:11][Cl:12])=[CH:8][C:7]=1[N+:1]([O-:4])=[O:2]
Reactant: Oc1ccc(CCCl)cc1
Reactant: O=[N+]([O-])O
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cc(CCCl)ccc1O
Reaction time: 3.5 h
Yield: 55 %

Procedure:
A solution of concentrated nitric acid (1.8 ml) in acetic acid (4 ml) was added to a stirred solution of 4-hydroxyphenethyl chloride (4.5 g) in acetic acid (25 ml), keeping the temperature below 15°. The mixture was then stirred at 10° for 3.5 hours, poured into water, and extracted into ethyl acetate. The organic extract was washed with 5% aqueous sodium carbonate solution, dried over magnesium sulphate and evaporated. The residue was purified by chromatography on silica (50 g) using hexane plus 0-10% ethyl acetate as the eluant. Appropriate fractions were combined and evaporated to give the title compound as a colourless solid (3.2 g, 55%), m.p. 53°-55°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2Cl.[CH3:18][N:19]([CH3:28])[CH:20]([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH3:21]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[N:25]1[CH2:26][CH2:27][CH:22]([CH:20]([N:19]([CH3:18])[CH3:28])[CH3:21])[CH2:23][CH2:24]1
Reactant: CC(C1CCNCC1)N(C)C
Reactant: O=C(c1cnc2ccc(Br)cc2c1Cl)C1CC1
Product: CC(C1CCN(c2c(C(=O)C3CC3)cnc3ccc(Br)cc23)CC1)N(C)C
Yield: 63.6 %

Procedure:
Following general procedure B, (6-bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone (300 mg, 0.965 mmol) was reacted with N,N-dimethyl-1-(piperidin-4-yl)ethanamine (332 mg, 1.45 mmol) to afford the desired product (264 mg, 63%) as a yellow solid: 1H NMR (300 MHz, CD3OD) δ 8.78 (s, 1H), 8.32 (s, 1H), 7.95-7.80 (m, 2H), 3.57-3.39 (m, 2H), 3.21 3.05 (m, 2H), 2.59-2.42 (m, 2H), 2.31 (s, 6H), 2.11-1.97 (m, 1H), 1.89 (d, J=12.4 Hz, 1H), 1.80-1.67 (m, 1H), 1.68-1.49 (m, 2H), 1.36-1.16 (m, 4H), 1.06 (d, J=6.6 Hz, 3H).
Reaction SMILES: [CH2:1]([OH:5])[CH2:2][CH2:3][OH:4].CC([O-])(C)C.[K+].Cl[C:13]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH:27]=[O:28])=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[CH:18]2>O>[OH:4][CH2:3][CH2:2][CH2:1][O:5][C:13]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]([CH:27]=[O:28])=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[CH:18]2
Reactant: O=Cc1c2ccccc2c(Cl)c2ccccc12
Reactant: OCCCO
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Product: O=Cc1c2ccccc2c(OCCCO)c2ccccc12
Reaction time: 2.5 h

Procedure:
To a 1 L 3-necked RB flask equipped with overhead stirrer, condenser, thermometer and N2 inlet line with bubbler was added 1,3-propanediol (Aldrich, 500 mL) and KOt-Bu (MCB, 14.03 g, 0.125 mol). After stirring for 30 min 10-chloro-9-anthracenecarbaldehyde (Aldrich, 25.0 g, 0.104 mol) was added to the flask and the mixture further stirred at 90° for 2.5 h. The reaction mixture was poured into H2O (5 L), filtered, dissolved in EtOAc, washed with H2O (3×500 mL), dried (Na2SO4), filtered and the solvent removed to give 24.98 g of dark oil. This was divided into two portions and each purified by preparative HPLC using SiO2 columns and EtOAc/CH2Cl2 (1:9) as the eluting solvent. Combination of the appropriate fractions followed by removal of the solvents by rotary evaporation gave 19.8 g (66%) of an orange solid, 10-[(3-hydroxy)propoxy]-9-anthracenecarbaldehyde, mp 72°-73°, (C,H).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1)[CH3:2].Cl[CH2:12][CH2:13][NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:12][CH2:13][NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: ClCCNCc1ccccc1
Reactant: CCOc1ccc(N)cc1
Product: CCOc1ccc(NCCNCc2ccccc2)cc1

Procedure:
In a manner similar to Preparation 29, react 4-ethoxybenzenamine with N-(2-chloroethyl)benzenemethanamine to obtain the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([S:20][C:21]([F:24])([F:23])[F:22])[CH:15]=1)(=[O:12])=[O:11])([O-])=O>C(O)C.O.[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([S:20][C:21]([F:24])([F:23])[F:22])[CH:15]=1)(=[O:12])=[O:11]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Nc1cccc(SC(F)(F)F)c1
Agent: [Pd]
Solvent: O
Solvent: CCO
Product: Nc1ccccc1S(=O)(=O)Nc1cccc(SC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 81.9 %

Procedure:
A solution of 2-nitro-N-{3-[(trifluoromethyl)sulfanyl]phenyl}benzenesulfonamide (605 mg, 1.6 mmol) in ethanol/H2O (4:1, 50 mL total reaction volume) was added to a suspension of 10% palladium on charcoal (50 mg) in ethanol/H2O (4:1) and the mixture stirred at rt under an atmosphere of H2 for approximately 2 d. After this time further 10% palladium on charcoal (75 mg) was added and the reaction mixture stirred under an atmosphere of H2 at rt for 3 h. Filtration and concentration in vacuo yielded the title compound (455 mg, 1.31 mmol).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[S:15])[NH:13][CH:14]=2)[CH3:8])[CH:2]=1.CI.[O-][CH2:20]C.[Na+]>C(O)C>[CH3:20][S:15][C:12]1[NH:11][C:10](=[O:16])[C:9]([CH:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH3:8])=[CH:14][N:13]=1
Reactant: CC(c1cccnc1)c1c[nH]c(=S)[nH]c1=O
Reactant: CC[O-]
Agent: [Na+]
Solvent: CI
Solvent: CCO
Product: CSc1ncc(C(C)c2cccnc2)c(=O)[nH]1

Procedure:
Treatment of 5-(1-(3-pyridyl)ethyl)-2-thiouracil with methyl iodide and sodium ethoxide in ethanol at 0°, followed by acidification gave 2-methylthio-5-[1-(3-pyridyl)ethyl]-4-pyrimidone m.p. 201°-204°.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[OH:13][C:14]1[CH:22]=[CH:21][C:17]([CH2:18][CH2:19][OH:20])=[CH:16][CH:15]=1>ClCCl>[CH3:8][S:9]([O:20][CH2:19][CH2:18][C:17]1[CH:21]=[CH:22][C:14]([O:13][S:9]([CH3:8])(=[O:11])=[O:10])=[CH:15][CH:16]=1)(=[O:11])=[O:10]
Reactant: CS(=O)(=O)Cl
Reactant: OCCc1ccc(O)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCc1ccc(OS(C)(=O)=O)cc1
Temperature: 25 °C
Yield: 88080.2 %

Procedure:
27.3 g (0.27 mmole) triethylamine and a solution of 27.2 g (0.239 g mmole) methane sulfonyl chloride in dichloromethane were added to a solution of 15 g (0.108 mmole) p-hydroxyphenethyl alcohol in dichloromethane at 0° C. The reaction was allowed to reach room temperature, then stirred at room temperature and followed by TLC. The reaction mixture was filtered and the filtrate was washed with water. The solution was dried with sodium sulfate and then evaporated in vacuo to give 28 g (yield 88%) of 4-(methylsulfonyloxy)phenethyl methanesulfonate.