Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.[OH-].[Na+].[CH2:20](Br)[CH3:21]>CO.O>[CH2:20]([O:1][C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1)[CH3:21]
Reactant: O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1O
Reactant: CCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CCOc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reaction time: 16 h
Yield: 52 %

Procedure:
The 2'-deoxy-5-hydroxyuridine (244 mg.,1 mmol) was suspended in a mixture of methanol (10 ml) and water (5 ml) at room temperature, and 1 ml of 1.0N sodium hydroxide solution (1 mmol) was added to generate the monoanion. Ethyl bromide (0.312 ml, 4 mmol) was added, and the reaction mixture was stirred for 16 hours. The solvent was removed in vacuo, and ethanol was added to and evaporated from the residue. The desired 5-ethoxy product was separated from small amounts of the 3-ethyl-5-ethoxy dialkyl byproduct by chromatography on a silica gel column using chloroform-methanol (9:1, v/v) as the solvent. Following crystallization from absolute ethanol, 5-ethoxy-2'-deoxyuridine was obtained in 52% yield (140mg); mp 179°-181° C.; 1H NMR (methyl sulfoxide-d6),δ6 11.38 (1H, br s, NH), 7.58 (1H, s, H-6), 6.18 (1H, t, H-1'), 5.19 (1H, d, 3'-OH), 5.09 (1H, t, 5'-OH), 4.25 (1H, m, H-3'), 3.79 (3H, m. H4' and OCH2CH3), 3.59 (2H, br s,H-5' and H-5"), 2.10 (2H, m, H-2' and H-2") and 1.23 ppm (3H, t, OCH2CH3).
Reaction SMILES: O=P(Cl)(Cl)Cl.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][C:16]=1[F:17])[NH:13][CH:12]=[CH:11]2.[OH-].[Na+].CN(C)[CH:22]=[O:23]>>[F:17][C:16]1[CH:15]=[C:14]2[C:10]([C:11]([CH:22]=[O:23])=[CH:12][NH:13]2)=[CH:9][C:8]=1[O:7][CH3:6]
Reactant: CN(C)C=O
Reactant: COc1cc2cc[nH]c2cc1F
Agent: [Na+]
Agent: [OH-]
Solvent: O=P(Cl)(Cl)Cl
Product: COc1cc2c(C=O)c[nH]c2cc1F
Temperature: 10 °C
Reaction time: 0.25 h
Yield: 95 %

Procedure:
POCl3 (10.9 ml, 71 mmol) is added dropwise to 21 ml of dimethylformamide under N2 at 10–20° C., is stirred 15 minutes, then a 13 ml dimethylformamide solution of 5-methoxy-6-fluoro-indole (J. Med. Chem., 22:63–69, 1979; 10.7 g, 64.7 mmol) is added at a rate to keep the reaction temperature between 10 and 20° C. After the addition is complete, the mixture is stirred for 1 hour. Crushed ice and aqeuous NaOH (12.5 g/50 ml H2O) is added to reaction. The resulting mixture is heated to reflux with a heat gun for 1 minute, cooled to 10° C., and is filtered to give 11.8 g of 6-fluoro-5-methoxy-1H-indole-3-carbaldehyde (95%).
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[C:6]([CH3:7])=[CH:5][CH2:4][CH:3]1[CH2:8][CH:9]=O.[CH3:12][C:13]1([CH3:27])[C:17]([CH3:18])=[CH:16][CH2:15][CH:14]1[CH2:19][CH:20]=[CH:21][C:22]([O:24]CC)=[O:23]>>[CH3:27][C:13]1([CH3:12])[CH:17]([CH3:18])[CH2:16][CH2:15][CH:14]1[CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23].[CH2:20]([CH:21]([CH2:9][CH2:8][CH:3]1[CH2:4][CH2:5][CH:6]([CH3:7])[C:2]1([CH3:11])[CH3:1])[C:22]([OH:24])=[O:23])[CH3:19]
Reactant: CC1=CCC(CC=O)C1(C)C
Reactant: CCOC(=O)C=CCC1CC=C(C)C1(C)C
Product: CC1CCC(CCCC(=O)O)C1(C)C
Product: CCC(CCC1CCC(C)C1(C)C)C(=O)O

Procedure:
4-(2,2,3-trimethylcyclopentyl)butanoic acid was synthesized in three steps; the first step reacts 2-(2,2,3-trimethylcyclopent-3-en-1-yl)acetaldehyde (aka campholenic aldehyde) to ethyl 4-(2,2,3-trimethylcyclopent-3-enyl)but-2-enoate, in the second step the latter was subjected to a hydrogenation procedure to form ethyl 4-(2,2,3-trimethylcyclopentyl)butanoic acid, and in the third step, from the latter, 4-(2,2,3-trimethylcyclopentyl)butanoic acid was formed in presence of sodium hydroxide (NaOH) and tetrahydrofuran (THF).
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[H-].[Na+].[F:10][C:11]1[C:16]([CH:17]([S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[S:18]([C:21]([F:24])([F:23])[F:22])(=[O:20])=[O:19])=[C:15]([F:32])[C:14]([F:33])=[C:13](F)[C:12]=1[F:35].O.Cl>N1C=CC=CC=1>[CH2:1]([O:7][C:13]1[C:12]([F:35])=[C:11]([F:10])[C:16]([CH:17]([S:18]([C:21]([F:24])([F:22])[F:23])(=[O:19])=[O:20])[S:25]([C:28]([F:29])([F:30])[F:31])(=[O:26])=[O:27])=[C:15]([F:32])[C:14]=1[F:33])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=S(=O)(C(c1c(F)c(F)c(F)c(F)c1F)S(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CCCCCCO
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Product: CCCCCCOc1c(F)c(F)c(C(S(=O)(=O)C(F)(F)F)S(=O)(=O)C(F)(F)F)c(F)c1F
Temperature: -20 °C
Reaction time: 5 h
Yield: 99 %

Procedure:
Hexanol (1.5 mL, 12 mmol) was added to a pyridine (10 mL) solution dissolved with 60% sodium hydride containing mineral oil (0.56 g, 14 mmol) at 0° C., and the resultant solution was stirred for 1 hour at room temperature. After the solution was cooled to −20° C., pentafluorophenylbis(triflyl)methane (0.89 g, 2 mmol) was added. The reaction solution was stirred at −20° C. for 5 hours. After the reaction, the solution was acidified with 4 M hydrochloric acid water, and was extracted with diethylether. After drying with magnesium sulfate, the solution was filtrated, and the solvent was removed under reduced pressure. The crude product was purified by sublimation (0.2 to 0.3 torr, 65° C.), and 4-hexanoxy-2,3,5,6-tetrafluorophenylbis(triflyl)methane was obtained at 99% yield (1.02 g, 1.98 mmol).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[C:10](Cl)(Cl)=[O:11].Cl.[CH3:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[C:26]([C:28]3[CH:37]=[C:36]4[C:31]([CH2:32][CH2:33][NH:34][CH2:35]4)=[CH:30][CH:29]=3)[N:25]=[C:24]([NH2:38])[N:23]=2)[CH2:18][CH2:17]1>>[NH2:38][C:24]1[N:25]=[C:26]([C:28]2[CH:37]=[C:36]3[C:31]([CH2:32][CH2:33][N:34]([C:10]([NH:1][C:2]4[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=4)=[O:11])[CH2:35]3)=[CH:30][CH:29]=2)[CH:27]=[C:22]([N:19]2[CH2:18][CH2:17][N:16]([CH3:15])[CH2:21][CH2:20]2)[N:23]=1
Reactant: CN1CCN(c2cc(-c3ccc4c(c3)CNCC4)nc(N)n2)CC1
Reactant: O=C(Cl)Cl
Reactant: N#Cc1ccc(N)nc1
Agent: Cl
Product: CN1CCN(c2cc(-c3ccc4c(c3)CN(C(=O)Nc3ccc(C#N)cn3)CC4)nc(N)n2)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 40 starting from 6-aminonicotinonitrile (Aldrich, Cat. #637475), phosgene and 4-(4-methylpiperazin-1-yl)-6-(1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidin-2-amine HCl salt. Analytic LCMS (M+H)+: m/z=470.2.
Reaction SMILES: C(O[C:6]([NH:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][C@@H:10]1[NH:19][C:20]([C:22]1[S:23][C:24]2[CH2:25][N:26]([CH3:31])[CH2:27][CH2:28][C:29]=2[N:30]=1)=[O:21])=[O:7])(C)(C)C.Cl.[Cl:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](C(O)=O)=[CH:37]2>O1CCOCC1>[ClH:33].[Cl:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38]([C:6]([NH:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][C@@H:10]1[NH:19][C:20]([C:22]1[S:23][C:24]3[CH2:25][N:26]([CH3:31])[CH2:27][CH2:28][C:29]=3[N:30]=1)=[O:21])=[O:7])=[CH:37]2
Reactant: COC(=O)[C@H]1CC[C@@H](NC(=O)OC(C)(C)C)[C@@H](NC(=O)c2nc3c(s2)CN(C)CC3)C1
Reactant: O=C(O)c1cc2cc(Cl)ccc2[nH]1
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)[C@H]1CC[C@@H](NC(=O)c2cc3cc(Cl)ccc3[nH]2)[C@@H](NC(=O)c2nc3c(s2)CN(C)CC3)C1

Procedure:
(1R*,2S*,4S*)-N1-tert-Butoxycarbonyl-4-methoxycarbonyl-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine was treated with a 4N dioxane solution of hydrochloric acid and then condensed with 5-chloroindole-2-carboxylic acid in a similar manner to Example 118 to obtain the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13](OC)=[C:12](F)[CH:11]=2)[CH:5]=[C:4]([Cl:19])[C:3]=1[N:20]=[CH:21][N:22]([CH3:24])[CH3:23].[F:25]C1C=CC=CC=1C=O.C(O)C.CCOCC>CCCCCC>[Cl:1][C:2]1[CH:7]=[C:6]([N:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:25])[CH:5]=[C:4]([Cl:19])[C:3]=1[N:20]=[CH:21][N:22]([CH3:24])[CH3:23]
Reactant: COc1ccc(C=Nc2cc(Cl)c(N=CN(C)C)c(Cl)c2)cc1F
Reactant: O=Cc1ccccc1F
Solvent: CCO
Solvent: CCCCCC
Solvent: CCOCC
Product: CN(C)C=Nc1c(Cl)cc(N=Cc2ccccc2F)cc1Cl

Procedure:
A mixture of 9.3 g. of N'-(4-amino-2,6-dichlorophenyl)-N,N-dimethylformamidine (Example 9) and 5.0 g. of o-fluorobenzaldehyde in 25 ml. of absolute ethanol is refluxed for 18 hours. The solution is evaporated in vacuo to provide a syrup. The syrup is dissolved in 50 ml. of ether and n-hexane is added to 500 ml. The solution is cooled and filtered. The filtrate is evaporated to 100 ml. to precipitate the product. The product is collected by filtration and washed with n-hexane to give 7.4 g. of the desired product as bright yellow crystals, m.p. 79°-81° C.
Reaction SMILES: Br[CH2:2][C:3]1[NH:8][C:7]([C:9]2[S:10][CH:11]=[N:12][N:13]=2)=[N:6][CH:5]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[C:4]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH:28]1[C:33]([OH:35])=[O:34]>>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[CH:5]1[N:6]=[C:7]([C:9]2[S:10][CH:11]=[N:12][N:13]=2)[NH:8][C:3]([CH2:2][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH:28]2[C:33]([OH:35])=[O:34])=[C:4]1[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: O=C(O)C1COCCN1
Reactant: CCOC(=O)C1=C(CBr)NC(c2nncs2)=NC1c1ccc(F)cc1F
Product: CCOC(=O)C1=C(CN2CCOCC2C(=O)O)NC(c2nncs2)=NC1c1ccc(F)cc1F
Yield: 40.5 %

Procedure:
Ethyl 6-(bromomethyl)-4-(2,4-difluorophenyl)-2-(1,3,4-thiadiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate (0.66 g, 1.5 mmol) was reacted with morpholine-3-carboxylic acid (0.2 g, 1.5 mmol) according to the procedure as described in Example 1, Step C to give the title compound as a yellow solid (0.3 g, 41%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: [C:1](=[O:23])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][CH:4]=1.[NH2:24][CH2:25][CH2:26][S:27]([O-:30])(=[O:29])=[O:28].[Na+].OC1C=CC(NC(=O)C)=CC=1.O>C(#N)C>[C:10]([NH:9][C:6]1[CH:5]=[CH:4][C:3]([O:2][C:1]([NH:24][CH2:25][CH2:26][S:27]([OH:30])(=[O:29])=[O:28])=[O:23])=[CH:8][CH:7]=1)(=[O:12])[CH3:11]
Reactant: NCCS(=O)(=O)[O-]
Reactant: CC(=O)Nc1ccc(OC(=O)Oc2ccc([N+](=O)[O-])cc2)cc1
Agent: CC(=O)Nc1ccc(O)cc1
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(=O)Nc1ccc(OC(=O)NCCS(=O)(=O)O)cc1

Procedure:
((4-Acetamidophenoxy)carbonylamino)ethanesulfonic acid (12a) was prepared according to the General Method for the Reaction of Alkali Metal Salts of Amino Acid Derivatives with 4-Acetamidophenyl 4-Nitrophenyl carbonate (3). A solution of 511 mg (3.48 mmol) of sodium 2-aminoethanesulfonate (7) in approximately one (1) mL of degassed water was reacted with a solution of 4-acetamidophenyl 4-nitrophenyl carbonate (3) (1.10 g, 3.48 mmol) dissolved in 5 mL of acetonitrile (MeCN). After work-up procedures, the aqueous layer was lyophilized off to afford 1.0 g (˜quantitative yield) of the crude 2-((4-acetamidophenoxy)carbonylamino)ethanesulfonic acid (12a) which was used directly and without further isolation or purification procedures. The material thus obtained was contaminated with some sodium chloride (NaCl) and other sodium salts. 1H NMR (300 MHz, D2O): δ 7.22 (d, J=9.0 Hz, 2H), 6.94 (d, J=8.7 Hz, 2H), 3.40 (t, J=6.6 Hz, 2H), 2.95 (t, J=6.6 Hz, 2H), 1.96 (s, 3H). LC/MS (ESI): m/z=303.0 [M+H]+, 602.8 [2M−H]−.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].CS(O[CH2:10][C@H:11]([C@@H:20]([C@H:29]([CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[O:30][S:31]([CH3:34])(=[O:33])=[O:32])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=O)=O>CN(C)C=O>[N:1]([CH2:10][C@H:11]([C@@H:20]([C@H:29]([CH2:35][O:36][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[O:30][S:31]([CH3:34])(=[O:33])=[O:32])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CS(=O)(=O)OC[C@@H](OCc1ccccc1)[C@H](OCc1ccccc1)[C@H](COCc1ccccc1)OS(C)(=O)=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)O[C@@H](COCc1ccccc1)[C@@H](OCc1ccccc1)[C@@H](CN=[N+]=[N-])OCc1ccccc1
Temperature: 60 °C
Yield: 68.2 %

Procedure:
A mixture of sodium azide (1.72 g, 26.4 mmol) and 1,4-di-O-methanesulfonyl-2,3,5-tri-O-benzyl-L-xylitol (13.9 g, 24 mmol) in dimethylformamide (500 mL) is heated overnight at 60° C. under stirring. Dimethylformamide is evaporated under reduced pressure. The residue is dissolved in ethyl acetate and washed with water. The organic layer is dried over sodium sulfate, filtered and concentrated under reduced pressure, yielding an oil. Flash chromatography on silica gel and elution with a 7:3 mixture of cyclohexane and ethyl acetate yield 1-azido-1-deoxy-4-O-methanesulfonyl -2,3,5-tri-O-benzyl-L-xylitol (8.6 g, 63%) as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11](Cl)=[O:12])[CH2:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:22]([NH2:25])[C:23]#[CH:24].C1C=CC=CC=1>O1CCCC1.O>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11]([NH:25][CH2:22][C:23]#[CH:24])=[O:12])[CH2:8]2)=[CH:4][CH:3]=1
Reactant: C#CCN
Reactant: O=C(Cl)N1CC(Oc2ccc(Cl)cc2)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: C#CCNC(=O)N1CC(Oc2ccc(Cl)cc2)C1
Reaction time: 16 h

Procedure:
A stirred mixture of 7.4 g (0.03 mole) of 3-(4-chlorophenoxy)-1-azetidinecarbonyl chloride and 4.5 g (0.03 mole) of potassium carbonate in 20 ml of tetrahydrofuran was treated with 1.7 g (0.03 mole) of 2-propynylamine added dropwise from a needle and syringe. After stirring for 16 hr, the reaction mixture was diluted with 400 ml of water and the resulting tan solid was collected by filtration, yielding 7.7 g of crude product. Repeated triturations of the crude product with hot benzene gave upon combining and cooling 1.2 g (15.2%) of tan powder, m.p. 120°-122° C.
Reaction SMILES: [C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:14][C:15]([C:17]2(CC(Cl)=C)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:16])[C:9]([N:11]([CH3:13])[CH3:12])=[O:10])=[CH:3][CH:2]=1.[O:32]=[O+][O-].C[C:36]([CH3:38])=[O:37]>>[C:1]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:14][C:15]([C:17]2([CH2:38][C:36]([OH:32])=[O:37])[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:16])[C:9]([N:11]([CH3:13])[CH3:12])=[O:10])=[CH:3][CH:2]=1
Reactant: O=[O+][O-]
Reactant: CC(C)=O
Reactant: C=C(Cl)CC1(C(=O)N[C@@H](Cc2ccc(-c3ccccc3)cc2)C(=O)N(C)C)CCCC1
Product: CN(C)C(=O)[C@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)C1(CC(=O)O)CCCC1
Temperature: -78 °C
Reaction time: 0.08 h

Procedure:
To a solution of (S)—N-(3-(biphenyl-4-yl)-1-(dimethylamino)-1-oxopropan-2-yl)-1-(2-chloroallyl)cyclopentanecarboxamide (78 mg, 0.18 mmol) in acetone (5 mL) at −78° C. was bubbled ozone for 1 minutes with a persistent pale blue color. The mixture was stirred at −78° C. for 5 minutes. To the mixture was bubbled oxygen for 10 minutes then added dimethyl sulfide (0.5 mL) followed by 1 mL of water. The mixture was stirred for 1 hr at room temperature and concentrated under reduced pressure. The obtained mixture was diluted in EtOAc and acidified with 1 M HCl. The organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) to give (S)-2-(1-(3-(biphenyl-4-yl)-1-(dimethylamino)-1-oxopropan-2-ylcarbamoyl)cyclopentyl)acetic acid (62 mg). HPLC retention time=1.54 minutes (condition D); MS (m+1)=423.1; 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 1.50-1.76 (m, 6H), 1.86-2.09 (m, 2H), 2.63 (s, 2H), 2.89 (s, 3H), 2.96-3.01 (m, 1H), 2.99 (s, 3H), 3.10 (dd, 1H), 5.00-5.20 (m, 1H), 6.95 (br. s., 1H), 7.31 (d, J=8.1 Hz, 2H), 7.35-7.44 (m, 1H), 7.48 (t, J=7.6 Hz, 2H), 7.58 (d, J=8.3 Hz, 2H), 7.62-7.72 (m, 2H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:12][S:13](=[S:16])([O-:15])=[O:14].[Na+].CN(C=O)C>O>[CH3:12][S:13](=[S:16])([O:15][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[O:14]
Reactant: CS(=O)([O-])=S
Reactant: CCCCCCCCCCBr
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCOS(C)(=O)=S
Temperature: 60 °C
Yield: 94 %

Procedure:
The mixture of 1-bromodecane (2.095 g, 0.00947 mol), sodium methanethiosulfonate and dry DMF (6 mL) was heated at 60° C. for 2 hr. At room temperature, water (15 mL) was added and the mixture was extracted with ether (3×30 mL). The ether extracts were washed with brine, dried, concentrated and the residue was subjected to flash column chromatography on silica gel with EtOAc-hexanes (1:4) to afford a white solid (2.063 g, 94%). It was recrystallized from 95% EtOH. mp: 28.0-29.5° C. IR (CDCl3 cast): 2954 (m), 2921 (st), 2852 (st), 1469 (m), 1305 (st), 1128 (st), 965 (m), 758 (m) and 720 cm−1 (m); 1H NMR (200 MHz, CDCl3): δ 3.32 (s, 3H, CH3SO2S), 3.17 (t, J=7.4 Hz, 2H, SCH2CH2), 1.77 (m, 2H, SCH2CH2), 1.50-1.20 (m, 14H, —(CH2)7—), 0.88 (m, 3H, CH2CH3); 13C NMR (50 MHz, CDCl3): δ 50.64, 36.49, 31.84, 29.45 (two carbons), 29.37, 29.23, 28.94, 28.57, 22.64, 14.08.
Reaction SMILES: [N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[NH:17][C:18]4[C:23]([C:24](=[O:26])[CH:25]=3)=[CH:22][C:21]([O:27][CH3:28])=[CH:20][C:19]=4[Br:29])=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:32][Si:33]([CH3:40])([CH3:39])[CH2:34][CH2:35][O:36][CH2:37]Cl.O>CN1CCCC1=O.CO>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:25]=[C:24]([O:26][CH2:37][O:36][CH2:35][CH2:34][Si:33]([CH3:40])([CH3:39])[CH3:32])[C:23]4[C:18](=[C:19]([Br:29])[CH:20]=[C:21]([O:27][CH3:28])[CH:22]=4)[N:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: COc1cc(Br)c2[nH]c(C(=O)Nc3ccc(N4CCOCC4)cc3)cc(=O)c2c1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: CN1CCCC1=O
Product: COc1cc(Br)c2nc(C(=O)Nc3ccc(N4CCOCC4)cc3)cc(OCOCC[Si](C)(C)C)c2c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 80.3 %

Procedure:
A yellow suspension of 8-bromo-6-methoxy-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide (Reference Example 27b) (3.092 g, 6.75 mmol) in 40 mL N-methylpyrolidinone was treated with sodium hydride (60% dispersion in oil, 0.410 g, 10.24 mmol). Gas evolution and warming were observed and the suspension became light brown and almost clear. The reaction was stirred for 10 minutes at room temperature under nitrogen. Addition of the 2-(trimethylsilyl)ethoxymethyl chloride (1.6 mL, 9.1 mmol) resulted in a slightly cloudy, lighter brown solution. After 4.5 hours at room temperature, the reaction mixture was poured into 300 mL water, stirred for 15 minutes and then stored at 0° C. overnight. The solids were isolated by filtration, suspended in methanol, filtered again, and dried under high vacuum to afford the product as a yellow solid (3.190 g, 80%). 1H NMR (300 MHz, DMSO, d6) δ 10.18 (s, 1 H, C(O)NH), 7.95 (d, 1 H, Jm=2.4 Hz, ArH7), 7.83 (s, 1 H, ArH3), 7.69 (d, 2 H, Jo=9.0 Hz, ArH2′& H6′), 7.51 (d, 1 H, Jm=2.7 Hz, ArH5), 7.00 (d, 2 H, Jo=9.0 Hz, ArH3′& H5′), 5.69 (s, 2 H, OCH2O), 3.95 (s, 3 H, OCH3), 3.85 (t, 2 H, J=8.0 Hz, OCH2CH2Si), 3.75 (t, 4 H, J=4.7 Hz, OCH2CH2N), 3.10 (t, 4 H, J=4.7 Hz, OCH2CH2N), 0.94 (t, 2 H, J=8.0 Hz, OCH2CH2Si), −0.04 (s, 9 H, Si(C H3)3; Mass Spec.: calc. for [C27H34BrN3O5Si+H]+ Theor. m/z=588, 590; Obs.=588, 590.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[OH:12])=[O:3].[CH3:13][N:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1.N1CCCC1>CO>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:4]2[C:2](=[O:3])[CH2:1][C:17]3([O:12][C:5]=2[CH:6]=1)[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]3
Reactant: CN1CCC(=O)CC1
Reactant: COc1ccc(C(C)=O)c(O)c1
Solvent: CO
Solvent: C1CCNC1
Product: COc1ccc2c(c1)OC1(CCN(C)CC1)CC2=O
Temperature: 25 °C
Reaction time: 7 h
Yield: 98.7 %

Procedure:
To a stirred solution of 2-hydroxy-4-methoxyacetophenone (4.08 g, 24.58 mmol) in anhydrous methyl alcohol (60 cm3) under an atmosphere of dry nitrogen was added 1-methyl-4-piperidinone (3 cm3, 24.58 mmol) followed by pyrrolidine (4 cm3, 47.92 mmol) and the solution was heated to reflux. After 7 h, a further portion of 1-methyl-4-piperidinone (0.6 cm3, 4.76 mmol) was added and the mixture was heated to reflux for a further 4.5 h. It was then allowed to cool to room temperature before the volatile fractions were removed under reduced pressure. The resulting oil was treated with dichloromethane (100 cm3), washed with water (5×100 cm3), dried over anhydrous sodium sulfate to afford a dark viscous oil (6.33 g, 24.25 mmol) which partially crystallised on standing over a long period of time.
Reaction SMILES: [N:1]([C:4]1[C:5](=[O:20])[NH:6][C:7]2[C:12]([C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N+:2]=[N-:3].[H-].[Na+].[CH3:23]N(C)C=O>>[N:1]([C:4]1[C:5](=[O:20])[N:6]([CH3:23])[C:7]2[C:12]([C:13]=1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=Nc1c(-c2ccccc2)c2ccccc2[nH]c1=O
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Product: Cn1c(=O)c(N=[N+]=[N-])c(-c2ccccc2)c2ccccc21
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a stirred suspension of 10.0 g of 3-azido-4-phenylcarbostyril in 125 ml. of dry dimethylformamide was added 2.2 g. of a 57 percent dispersion of sodium hydride in oil. After stirring at room temperature for about 45 minutes, the mixture was filtered to remove a small amount of insoluble material. To the clear solution was added 5 ml. of methyl iodide. The solution soon turned from an orange color to light yellow, accompanied by the formation of a precipitate. After 1 hour, the mixture was diluted with water and 10 g. (95 percent) of 3-azido-1-methyl-4-phenylcarbostyril, mp indefinite in the range of 140°-150° with decomposition, was collected. This material was pure by tlc. After recrystallizations from dimethylformamide-methanol, yellow needles were obtained, having a melting point of 140°-150° dec.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH3:13])=[C:7]([OH:9])[CH:8]=1.C(N(CC)CC)C.[Br:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[C:28](=[O:32])[NH:27][C:26](=[O:33])/[C:25]/2=[CH:34]/OC.O>CN(C)C=O>[Br:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[C:28](=[O:32])[NH:27][C:26](=[O:33])/[C:25]/2=[CH:34]\[NH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH3:13])=[C:7]([OH:9])[CH:8]=1
Reactant: CO/C=C1/C(=O)NC(=O)c2ccc(Br)cc21
Reactant: CCCOc1ccc(CN)cc1O
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: CCCOc1ccc(CN/C=C2\C(=O)NC(=O)c3ccc(Br)cc32)cc1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 28.2 %

Procedure:
According to the general procedure of example 129, an amount of 100 mg (0.55 mmol) of 5-(aminomethyl)-2-propoxyphenol is dissolved in N,N-dimethylformamide (5 mL). 228 μl (1.65 mmol) of triethylamine is added followed by 171 mg (0.607 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (3 mL) is added and the reaction mixture is stirred for 3 hours. The precipitate is filtered and washed several times with anhydrous ether. The crude solid is then purified by high performance liquid chromatography to give 67 mg of a white solid. MS (ESI) m/z 430.8 (M+1).