Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16](Cl)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][O-:22].[Na+]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16]([O:22][CH3:21])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[O-]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cncc(Cl)n2)CC1
Agent: [Na+]
Product: COc1cncc(N2CCN(C(=O)OC(C)(C)C)CC2)n1

Procedure:
1 mmol of 6′-Chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester [example 4.9 (a)] was dissolved in a solution of sodium methanolate (prepared by dissolving 1 mmol of sodium in 10 ml of methanol). The mixture was heated overnight to 70°, concentrated and the product purified by chromatography (SiO2; dichloromethane/methanol 99:1) to yield the title compound as a colorless foam. MS (m/e): 295.3 (MH+, 100%)
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].[C:26]1([S:32]([C:35]2[CH:36]=[C:37](OS(C(F)(F)F)(=O)=O)[C:38](=[O:44])[N:39]3[C:43]=2[CH2:42][CH2:41][CH2:40]3)(=[O:34])=[O:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(N(CC)CC)C.C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:26]1([S:32]([C:35]2[CH:36]=[C:37]([C:25]#[C:24][Si:21]([CH3:23])([CH3:22])[CH3:20])[C:38](=[O:44])[N:39]3[C:43]=2[CH2:42][CH2:41][CH2:40]3)(=[O:34])=[O:33])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: C#C[Si](C)(C)C
Reactant: O=c1c(OS(=O)(=O)C(F)(F)F)cc(S(=O)(=O)c2ccccc2)c2n1CCC2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1cc(S(=O)(=O)c2ccccc2)c2n(c1=O)CCC2
Temperature: 25 °C

Procedure:
Pyridinone derivative (P) can also be derivatized to form pyridinone derivative (W) by the organometallic coupling of (trimethylsilyl)acetylene as shown in Reaction Scheme XIII. A similar result in Reaction Scheme XIII can be obtained for the corresponding derivative of pyridinone (E). wherein Z, R2, R3, and R4 are as defined in Reaction Scheme VI. Reagents for the organometallic coupling include PdCl2(PPh3)2 and Cul or other suitable organometallic reagents. The organometallic coupling is accomplished by combining the halogenated pyridinone derivative with (trimethylsilyl)acetylene and triphenylphosphine, PdCl2(PPh3)2 and Cul and then heating at 120 degrees Celcius for 72 hours. The preparation of pyridinone derivative (W) is illustrated by a procedure described by Padwa A., Sheehan S. M., and Straub C. S., J. Org. Chem. 1999, 64: 8648-8659 for an isomunchnone-based method for the synthesis of highly substituted 2(1H)-pyridones, the entirety of which is hereby incorporated by reference. The authors describe the palladium catalyzed coupling of (trimethylsilyl)acetylene with a triflate to provide a (trimethylsilyl)acetylene substituted compound. The specific preparation procedure employed by the authors involved the addition of Cul, followed by PdCl2(PPh3)2 to a solution containing triphenylphosphine in triethylamine. To this solution was added (trimethylsilyl)acetylene in toluene followed by the addition of trifluoromethanesulfonic acid 8-phenylsulfonyl-5-oxo-1,2,3,5-tetrahydroindolizin-6-yl ester. The mixture was heated at 115 degrees Celcius for 1 hour, cooled to room temperature, poured into ice water, extracted with CH2Cl2, washed with brine, and dried over Na2SO4. The organic extracts were filtered and concentrated under reduced pressure. The crude residue was subjected to flash silica gel chromatography to yield 8-phenylsulfonyl-6-trimethylsilanylethynyl-2,3-dihydro-1H-indolizin-5-one.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][CH:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=2)[CH2:15][CH2:14][NH:13]1.Br[CH2:27][C:28](Br)=[O:29].[NH2:31][CH:32]1[CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33]1>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][CH:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:27][C:28]([NH:31][CH:32]1[CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33]1)=[O:29]
Reactant: O=C(Br)CBr
Reactant: COc1cc2c(cc1OC)C(Cc1ccc3ccccc3c1)NCC2
Reactant: NC1Cc2ccccc2C1
Product: COc1cc2c(cc1OC)C(Cc1ccc3ccccc3c1)N(CC(=O)NC1Cc3ccccc3C1)CC2

Procedure:
prepared by reaction of 1-(Naphthalen-2-yl-methyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and 2-bromoacetyl bromide with 2-amino-indane
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[CH3:25]>>[F:17][C:4]1[CH:3]=[C:2]([C:21]2[CH:22]=[CH:23][C:24]([CH3:25])=[C:19]([F:18])[CH:20]=2)[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=1
Reactant: Cc1ccc(B(O)O)cc1F
Reactant: Cc1c2n(c3c(Br)cc(F)cc13)CCNC2=O
Product: Cc1ccc(-c2cc(F)cc3c(C)c4n(c23)CCNC4=O)cc1F

Procedure:
The title compound, light yellow solid (71 mg, 87%), MS (ISP) m/z=327.5 [(M+H)+], mp 206° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-fluoro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 14) (74.3 mg, 0.25 mmol) and commercially available 3-fluoro-4-methyl-phenylboronic acid (50.0 mg, 0.325 mmol).
Reaction SMILES: [CH3:1][C:2]([O:25]C1CCCCO1)([CH2:20][CH2:21][C:22]#[C:23][CH3:24])/[CH:3]=[CH:4]/[C@@H:5]1[C@@H:9]([CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])[C:8](=[O:19])[CH2:7][CH2:6]1>C(O)(=O)C.O.C1COCC1>[OH:25][C:2]([CH3:1])([CH2:20][CH2:21][C:22]#[C:23][CH3:24])/[CH:3]=[CH:4]/[C@@H:5]1[C@@H:9]([CH2:10]/[CH:11]=[CH:12]\[CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])[C:8](=[O:19])[CH2:7][CH2:6]1
Reactant: CC#CCCC(C)(/C=C/[C@H]1CCC(=O)[C@@H]1C/C=C\CCCC(=O)O)OC1CCCCO1
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: CC#CCCC(C)(O)/C=C/[C@H]1CCC(=O)[C@@H]1C/C=C\CCCC(=O)O

Procedure:
300 mg. of (5Z,13E)-(15RS)-15-methyl-9-oxo-15-(tetrahydropyran-2-yloxy)-5,13-prostadien-18-ynoic acid is agitated for 16 hours at room temperature with 8 ml. of a mixture of glacial acetic acid/water/THF (65/35/10); the mixture is then evaporated under vacuum, and the residue is purified by chromatography on silica gel. With methylene chloride/5% methanol, 205 mg. of the title compound is obtained as a colorless oil.
Reaction SMILES: C(O)(=O)CCCCCCCCC(O)=O.NCCNCCNCCNCCNCCN.O[CH:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])[C:33](O)=[O:34].NCCNCCNCCN.C(C1OC1)Cl>O.C(O)(=O)C>[CH2:36]([CH:32]=[C:33]=[O:34])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51]
Reactant: CCCCCCCCCCCCCCCCC(O)C(=O)O
Agent: NCCNCCNCCN
Agent: NCCNCCNCCNCCNCCN
Agent: O=C(O)CCCCCCCCC(=O)O
Solvent: ClCC1CO1
Solvent: O
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCCCC=C=O

Procedure:
Except that 60.5 g of castor oil fatty acid, 20.2 g of sebacic acid and 48.7 g of pentaethylenehexamine were used instead of hydroxystearic acid and triethylenetetramine, the same procedures and conditions as those used in the foregoing Example 1 were repeated to subject the input materials to a reaction. At the end of the reaction, 54 g of glacial acetic acid was added thereto, followed by dilution with warm water. Then, after adding 7.4 g of epichlorohydrin thereto, the resultant system was subjected to a reaction at 80°-85° C. for 2 hours to produce a dispersion having a solid content of 20% by weight. Hereinafter, this dispersion shall be referred to as the dispersing agent Hs according to the present invention. Thereafter, by using 10 parts by weight, as solid content, of the dispersing agent Hs, a dispersion of hexadecyl ketene dimer was prepared in the same manner as in the preceding Example 7. Hereinafter, this dispersion shall be referred to as the cellulose treating agent H according to the present invention.
Reaction SMILES: [CH:1]1([O:7][C:8]2[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([S-])C.[Na+].O.Cl>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([O:7][C:8]2[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COc1ccc(OC2CCCCC2)cc1
Agent: CC[S-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Oc1ccc(OC2CCCCC2)cc1
Temperature: 25 °C
Yield: 45.8 %

Procedure:
To 1-cyclohexyloxy-4-methoxy-benzene (2.06 g, 10 mmol), prepared in accordance with the procedure of He, et. al., J. Am. Chem. Soc., 2005, 127, 6966, in DMF (20 mL) was added sodium ethanethiolate (1.15 g, 11 mmol). The reaction mixture was stirred at reflux for two hours. The reaction mixture was then cooled to room temperature. Water (5 mL) was added after which the mixture was neutralized with hydrochloric acid (2N). Ethyl acetate (200 mL) was then added and the organic phase washed with water three times, brine twice, and dried (Na2SO4). Silica gel chromatography (EtOAc/heptane) provided 0.88 g of the title compound.
Reaction SMILES: [CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]([O:24]C(C)(C)C)=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7]2[CH:29]=[C:30]([C:34]3[N:35]=[CH:36][N:37]([CH2:39][C:40]([F:43])([F:42])[F:41])[CH:38]=3)[CH:31]=[C:32]([CH3:33])[C:6]=2[N:5]=1)[CH2:2][CH3:3].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7]2[CH:29]=[C:30]([C:34]3[N:35]=[CH:36][N:37]([CH2:39][C:40]([F:41])([F:42])[F:43])[CH:38]=3)[CH:31]=[C:32]([CH3:33])[C:6]=2[N:5]=1)[CH2:2][CH3:3]
Reactant: CCCc1nc2c(C)cc(-c3cn(CC(F)(F)F)cn3)cc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCc1nc2c(C)cc(-c3cn(CC(F)(F)F)cn3)cc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared analogously to Example 88 from tert.butyl 4'-[(2-n-propyl-4-methyl-6-(1-(2,2,2-trifluoroethyl)-imidazol-4-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylate and trifluoroacetic acid in methylene chloride.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[NH:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:11]OC(=O)OC.CCN(CC)CC>C(OCC)(=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]([CH3:11])[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1
Reactant: COC(=O)OC
Reactant: Brc1cnc2cc[nH]c2c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: Cn1ccc2ncc(Br)cc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 83.7 %

Procedure:
A solution of 6-bromo-1H-pyrrolo[3,2-b]pyridine (54 kg from multiple batches based on wt % assay, 274 mol) in ethyl acetate from the previous step was distilled under vacuum at 45±5° C. to a volume of about 110 L (2 L/kg) and then cooled to 25±5° C. Dimethylcarbonate (33.0 kg, 367 mol) and Et3N (22.0 kg, 217 mol) were added and the mixture was distilled under vacuum at 50±5° C. to a volume of about 85 L. N,N-dimethylformamide (82.5 kg, 1.6 L/kg) was added and the mixture was distilled under vacuum at 50±5° C. until no distillate was observed. The mixture was cooled to 25±5° C., and dimethylcarbonate (165 kg, 1833 mol), Et3N (60.5 kg, 598 mol), and tetrabutylammonium bromide (11.0 kg) were added. The reaction mixture was heated to 88±5° C. After 12 hours at 105-110° C. (jacket temperature), which corresponded to 83-85° C. reaction mixture temperature, HPLC analysis indicated 59.6% of the starting material remained. The jacket temperature was increased to 115-120° C. (corresponding to 84-87° C. reaction mixture temperature). After 18 hours at 115-120° C. (jacket temperature) HPLC analysis indicated 0.2% of the starting material remained. The mixture was cooled to 25° C. and then concentrated under vacuum at 55±5° C. to remove most of the dimethylcarbonate and Et3N. Next, the mixture was cooled to 25° C. and MTBE (340 kg) was added, followed by water (440 kg). The mixture was stirred for 30 minutes. Stirring was stopped and the mixture was left for 30 minutes for phase separation to occur. The aqueous phase was extracted with MTBE (2×209 kg). The MTBE phases were combined and washed with brine solution (286 kg). Activated charcoal (2.7 kg) was added to the organic phase, which was stirred for 1 hour and then filtered through a pad of Celite. The filter cake was washed with MTBE (55 kg). The organic layers were combined (750 kg, 6.45% by HPLC-assay) and distilled to dryness to obtain the title compound as yellow oil (48.4 kg). The product was used directly in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:14])[NH:12][CH3:13])[CH:8]=[C:7]([Cl:15])[C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[CH3:20][C:21]1[NH:35][C:24]2=[C:25]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:26]=[CH:27][CH:28]=[C:23]2[CH:22]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl.CO>[Cl:15][C:7]1[CH:8]=[C:9]([CH:10]=[C:2]([Cl:1])[C:3]=1[C:4]([C:22]1[C:23]2[C:24](=[C:25]([NH:29][C:30]([CH:32]3[CH2:33][CH2:34]3)=[O:31])[N:26]=[CH:27][CH:28]=2)[NH:35][C:21]=1[CH3:20])=[O:6])[C:11]([NH:12][CH3:13])=[O:14]
Reactant: CNC(=O)c1cc(Cl)c(C(=O)O)c(Cl)c1
Reactant: Cc1cc2ccnc(NC(=O)C3CC3)c2[nH]1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=S(Cl)Cl
Solvent: CO
Solvent: ClCCl
Product: CNC(=O)c1cc(Cl)c(C(=O)c2c(C)[nH]c3c(NC(=O)C4CC4)nccc23)c(Cl)c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 28.6 %

Procedure:
To a solution of 2,6-dichloro-4-(methylcarbamoyl)benzoic acid (276 mg, 1.1 mmol) in dry dichloromethane, was added thionyl chloride (5 mL) and heated at 100° C. for about 3 hours. The mixture was concentrated under vacuum. The residue was dissolved in dry dichloromethane (3 mL) and added to the stirred solution of N-(2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)cyclopropanecarboxamide (120 mg, 0.55 mmol) in aluminium chloride (743 mg, 5.57 mmol) drop wise. The resulting reaction mixture was stirred overnight at room temperature. After completion, methanol (10 mL) was added cautiously to quench the reaction mass followed by concentration under vacuum. The reaction mass was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with aq. sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate, and concentrated. Purification by silica gel (100-200) column chromatography using dichloromethane and methanol gradient as eluent afforded 3,5-dichloro-4-({7-[(cyclopropylcarbonyl)amino]-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl}carbonyl)-N-methylbenzamide (70 mg, 29%).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[C:16]([O:34][CH3:35])=[C:17]([CH:23]4[CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24]4)[C:18]([CH3:22])=[C:19]([Cl:21])[CH:20]=3)[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[ClH:36].O1CCOCC1>C(Cl)Cl>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[CH:20]=[C:19]([Cl:21])[C:18]([CH3:22])=[C:17]([CH:23]4[CH2:26][NH:25][CH2:24]4)[C:16]=3[O:34][CH3:35])[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[ClH:36]
Reactant: COc1c(C(C)n2ccc(=O)c3c(N)ncnc32)cc(Cl)c(C)c1C1CN(C(=O)OC(C)(C)C)C1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: COc1c(C(C)n2ccc(=O)c3c(N)ncnc32)cc(Cl)c(C)c1C1CNC1

Procedure:
A solution of tert-butyl 3-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidine-1-carboxylate (27 mg, 0.053 mmol) in methylene chloride (0.25 mL) was treated with 4.0 M hydrogen chloride in dioxane (0.13 mL, 0.50 mmol) at room temperature for 1 hour, then stripped to dryness to give 4-amino-8-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]pyrido[2,3-d]pyrimidin-5(8H)-one as HCl salt.
Reaction SMILES: C[O:2][C:3](=[O:39])[CH2:4][N:5]([CH2:34][C:35]([O:37]C)=[O:36])[C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:9]=[C:8]([N+:31]([O-:33])=[O:32])[CH:7]=1.[OH-].[Na+]>CO.O1CCOCC1.O>[C:3]([CH2:4][N:5]([C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:9]=[C:8]([N+:31]([O-:33])=[O:32])[CH:7]=1)[CH2:34][C:35]([OH:37])=[O:36])([OH:39])=[O:2]
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(N(CC(=O)OC)CC(=O)OC)cc([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCOc1cc(N(CC(=O)O)CC(=O)O)cc([N+](=O)[O-])c1
Temperature: 25 °C
Yield: 80.9 %

Procedure:
A solution of 1.44 g (2.6 mmol) of N-(2-methoxy-2-oxoethyl)-N-[3-nitro-5-(octadecyloxy)phenyl]glycine methyl ester and 15 ml of 1N NaOH in 65 ml of methanol, 10 ml of dioxane and 20 ml of water was stirred reflux for 5 hours. The solvents were removed at reduced pressure and the residue was dissolved in 400 ml of hot water. After cooling to room temperature, 6N HCl was added to acidify and the resultant precipitate was filtered. Purification by chromatography on 40 g of silica gel using 20% methanol-chloroform gave 1.1 g (81% yield, mp 131°-134°) of N-(carboxymethyl)-N-[3-nitro-5-(octadecyloxy)phenyl]glycine.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.Br[CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1>C(Cl)(Cl)Cl>[NH:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([CH2:13][CH2:12][N:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)=[CH:15]1
Reactant: c1ccc2c(c1)CCCN2
Reactant: BrCCc1c[nH]c2ccccc12
Solvent: ClC(Cl)Cl
Product: c1ccc2c(c1)CCCN2CCc1c[nH]c2ccccc12

Procedure:
1,2,3,4-Tetrahydroquinoline (5.94 g, 5.6 ml, 44.6 mmol) was added to a solution of 3-(2-bromoethyl)-indole (5.00 g, 22.3 mmol) in dry chloroform (25 ml) at room temperature and the mixture was then stirred under reflux for 5 h. The reaction mixture cooled overnight. The organic phase was extracted with dil. sulfuric acid (2×50 ml). The aqueous phase was rendered basic with 5N NaOH, while cooling with ice, and extracted with ether (3×50 ml). The organic phase was dried over Na2SO4 and concentrated i. vac. Yield: 5.35 g (Ind-62, 88%)
Reaction SMILES: BrCC1C=CSN=1.C(N)CN.[S:12]1[CH:16]=[CH:15][C:14]([CH2:17][NH:18][CH2:19][CH2:20][NH2:21])=[N:13]1.[CH3:22][N:23]=[C:24]=[S:25]>>[CH3:22][NH:23][C:24]([NH:21][CH2:20][CH2:19][NH:18][CH2:17][C:14]1[CH:15]=[CH:16][S:12][N:13]=1)=[S:25]
Reactant: NCCNCc1ccsn1
Reactant: CN=C=S
Agent: BrCc1ccsn1
Solvent: NCCN
Product: CNC(=S)NCCNCc1ccsn1

Procedure:
Reaction of 3-bromomethylisothiazole with ethylenediamine by the procedure of Example 34 and reaction of the resulting N-(3-isothiazolylmethyl)ethylenediamine with methyl isothiocyanate by the procedure of Example 3(b) and then chromatographing gives N-methyl-N'[2-(3-isothiazolylmethylamino)ethyl]thiourea. This intermediate is reacted with lead cyanamide by the procedure of Example 3(b) to give N-cyano-N'[2-(3-isothiazolylmethylamino)ethyl]-N"-methylguanidine. Hydrolysis of the last prepared compound by the procedure of Example 3(e) gives N-[2-(3-isothiazolylmethylamino)ethyl]-n'-methylguanidine dihydrochloride.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C[O-].[Na+].CO.[Cl:14][C:15](Cl)=[CH:16][C:17]([CH3:20])([CH3:19])[CH3:18]>CN(C)C=O.C(Cl)Cl>[Cl:14][CH:15]=[C:16]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:17]([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)C=C(Cl)Cl
Reactant: Oc1ccc(Cl)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)(C)C(=CCl)Oc1ccc(Cl)cc1
Yield: 81.6 %

Procedure:
26 g (0.2 mol) of p-chlorophenol were reacted with 40 ml of 30% strength sodium methylate solution (0.2 mol) in 150 ml of dimethylformamide. After the methanol had been stripped off, a further 50 ml of dimethylformamide were distilled off under 20 mbar. 15.3 g (0.1 mol) of 1,1-dichloro-3,3-dimethyl-1-butene were then added and the mixture was heated under reflux for 18 hours. The solution was diluted with methylene chloride and extracted three times by shaking with dilute sodium hydroxide solution. The organic phase was dried over sodium sulphate and the solvent was removed in vacuo. Distillation gave dimethylformamide in the first runnings, and 20 g of 1-chloro-3,3-dimethyl-2-(4'-chlorophenoxy)-1-butene, that is to say 81% of theory, as the main fraction at boiling point 110°-128° C./0.15 mm Hg. NMR (CDCl3): δ 1.15 (s, 9H), 5.9 (s, 1H) and 6.8- 7.4 (m, 4H). ##STR9##
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2)#[N:2].[Cl:13][C:14]1[N:19]=[CH:18][C:17]([S:20]([N:23]2[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]2)(=[O:22])=[O:21])=[CH:16][CH:15]=1>>[ClH:13].[OH:12][C:7]1[NH:8][C:9]2[C:5]([C:6]=1[C:14]1[CH:15]=[CH:16][C:17]([S:20]([N:23]3[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]3)(=[O:22])=[O:21])=[CH:18][N:19]=1)=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=2
Reactant: N#Cc1ccc2c(c1)CC(=O)N2
Reactant: CC(C)N1CCN(S(=O)(=O)c2ccc(Cl)nc2)CC1
Product: CC(C)N1CCN(S(=O)(=O)c2ccc(-c3c(O)[nH]c4ccc(C#N)cc34)nc2)CC1
Product: Cl
Yield: 30 %

Procedure:
The title compound was prepared as described for Example 82 using 5-cyanooxindole and 1-[(6-chloropyridin-3-yl)sulfonyl]-4-isopropylpiperazine. Yield: 30% of the title compound as a yellow solid; 1H NMR (DMSO-d6, 400 MHz) δ 11.56 (br s, 1 H), 10.68 (br s, 1 H), 8.57 (br s, 1 H), 8.02 (s, 1 H), 7.93-7.81 (m, 1 H), 7.74 (dd, J=9, 2 Hz, 1 H), 7.42 (dd, J=8, 1 Hz, 1 H), 7.06 (d, J=8 Hz, 1 H) 3.82-3.71 (m, 2 H), 3.58-3.31 (m, 3 H), 3.24-1.82 (m, 4 H), 1.24 (d, J=7 Hz, 6 H); MS (ES) m/z 304 (M++1).
Reaction SMILES: O.[OH-].[Li+].[CH2:4]([CH:6]([CH2:34][CH3:35])[CH2:7][NH:8][C:9]([C:11]1[CH:20]=[C:19]2[C:14]([CH:15]=[CH:16][CH:17]=[C:18]2[CH2:21][C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][C:23]=2[O:32][CH3:33])=[CH:13][CH:12]=1)=[O:10])[CH3:5].CO.O1CCCC1>O>[CH2:34]([CH:6]([CH2:4][CH3:5])[CH2:7][NH:8][C:9]([C:11]1[CH:20]=[C:19]2[C:14]([CH:15]=[CH:16][CH:17]=[C:18]2[CH2:21][C:22]2[CH:31]=[CH:30][C:25]([C:26]([OH:28])=[O:27])=[CH:24][C:23]=2[O:32][CH3:33])=[CH:13][CH:12]=1)=[O:10])[CH3:35]
Reactant: CCC(CC)CNC(=O)c1ccc2cccc(Cc3ccc(C(=O)OC)cc3OC)c2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CCC(CC)CNC(=O)c1ccc2cccc(Cc3ccc(C(=O)O)cc3OC)c2c1
Reaction time: 18 h
Yield: 73.7 %

Procedure:
A solution of lithium hydroxide monohydrate (150 mg) in water (4 ml) was added to a solution of methyl 4-(7-(2-ethylbutylcarbamoyl)naphth-1-ylmethyl)-3-methoxybenzoate (310 mg) in 1:1 methanol:tetrahydrofuran (15 ml). The mixture was stirred for 18 h. After most of the solvent was evaporated, water (7 ml) was added. The mixture was acidified with 1N hydrochloric acid and the precipitate was filtered, triturated with 25 ml of 10:1 ether:methanol, ground to a powder and vacuum dried at 100° C for 12 h to give 4-[7-(2-ethylbutylcarbamoyl)naphth-1-ylmethyl]-3-methoxybenzoic acid (221 mg, 74%) as a colorless solid; mp 198.0°-199.0° C.