Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[CH2:9][CH:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.[H-].[Na+].N1(P(Cl)(N2CCOCC2)=O)CCOCC1.[C:37]([NH:40][NH2:41])(=O)[CH3:38]>O1CCCC1.C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:37]([CH3:38])=[N:40][N:41]=[C:10]3[CH2:9][CH:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1
Reactant: O=C1CC=C(c2ccccc2)c2cc(Cl)ccc2N1
Reactant: CC(=O)NN
Agent: O=P(Cl)(N1CCOCC1)N1CCOCC1
Agent: [H-]
Agent: [Na+]
Solvent: CCCCO
Solvent: C1CCOC1
Product: Cc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=CC2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 1.075 g of 7-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one in 20 ml of dry tetrahydrofuran is treated with 0.23 g of sodium hydride (50% dispersion in mineral oil) and stirred at 60° for 1 hour. The mixture is then cooled to room temperature, treated with 1.53 g of bis-(4-morpholinyl)phosphinic acid chloride and stirred at this temperature for a further 2 hours. A solution of 0.593 g of acetic acid hydrazide in 50 ml of n-butanol is subsequently added thereto, the mixture is heated to boiling under reflux for 1 hour and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The methylene chloride solution is evaporated and the residue is chromatographed on 100 g of aluminium oxide (activity grade III). Various impurities and starting material are eluted successively with benzene and ethyl acetate/hexane (1:1). After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane, there is obtained 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine of melting point 235°.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:19][CH:18]=2)[CH:10]=1.I[CH2:30][CH2:31][CH3:32].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([CH2:30][CH2:31][CH3:32])[C:17]2[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:21][CH:22]=2)[CH:10]=1
Reactant: CCCI
Reactant: COC(=O)CCc1ccc(NCc2cccc(-c3c(C)cccc3C)c2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCN(Cc1cccc(-c2c(C)cccc2C)c1)c1ccc(CCC(=O)OC)cc1
Temperature: 90 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
To a solution of methyl 3-(4-{[(2′,6′-dimethylbiphenyl-3-yl)methyl]amino}phenyl)propanoate (0.747 g, 2.00 mmol) and 1-iodopropane (0.585 mL, 6.00 mmol) in N,N-dimethylformamide (3 mL) was added potassium carbonate (0.415 g, 3.00 mmol), and the mixture was stirred under a nitrogen atmosphere at 90° C. for 8 hr. After cooling, the reaction mixture was concentrated under reduced pressure. Water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-20% ethyl acetate/hexane) to give the title compound (0.740 g, yield 89%) as a yellow oil.
Reaction SMILES: [C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]3[CH2:12][NH:13][CH2:14][CH2:15][N:10]3[C:9](=[O:16])[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=O)C.[CH2:27]([N:34]1[CH2:39][CH2:38][C:37](=O)[CH2:36][CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.O>[C:17]1([C:7]2([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:11]3[CH2:12][N:13]([CH:37]4[CH2:36][CH2:35][N:34]([CH2:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH2:39][CH2:38]4)[CH2:14][CH2:15][N:10]3[C:9](=[O:16])[O:8]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: O=C1OC(c2ccccc2)(c2ccccc2)C2CNCCN12
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: O=C1OC(c2ccccc2)(c2ccccc2)C2CN(C3CCN(Cc4ccccc4)CC3)CCN12
Temperature: 25 °C
Reaction time: 16 h
Yield: 29.4 %

Procedure:
To a solution of hexahydro-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazin-3-one (0.15 g, 0.51 mmol), acetic acid (0.045 mL, 0.79 mmol) and 1-benzyl-4-piperidone (0.12 g, 0.63 mmol) in tetrahydrofuran (5 mL) was added sodium triacetoxyborohydride (0.16 g, 0.75 mmol), and the mixture was stirred at room temperature for 16 hours. 1-Benzyl-4-piperidone (0.060 mL) and sodium triacetoxyborohydride (0.16 g) were added thereto, and the mixture was stirred at room temperature for 3 days. The reaction solution was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogen carbonate solution, water and saturated brine, and then dried over magnesium sulfate. The solid was filtered off, and the filtrate was concentrated. The residue was purified with amino silica gel column chromatography (hexane:ethyl acetate=98:2 to hexane:ethyl acetate=1:1) and recrystallized from ethyl acetate-hexane to obtain the title compound (70 mg, yield 29%).
Reaction SMILES: [CH3:1][C:2]([CH3:12])([C:4](=[O:11])[CH2:5][N:6]1[CH:10]=[N:9][CH:8]=[N:7]1)[CH3:3].[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(OC(C)C)(C)C>CN(C)C=O.O>[CH3:3][C:2]([CH3:12])([C:4](=[O:11])[CH:5]([N:6]1[CH:10]=[N:9][CH:8]=[N:7]1)[CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:1]
Reactant: BrCCCCOc1ccccc1
Reactant: CC(C)(C)C(=O)Cn1cncn1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CC(C)OC(C)C
Product: CC(C)(C)C(=O)C(CCCCOc1ccccc1)n1cncn1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of 14.3 g of 2,2-dimethyl-4-(1,2,4-triazol-1-yl)-butan-3-one (cf. German Laid-Open Application DOS No. 2,638,470) in 20 ml of DMF is added dropwise, under a dry nitrogen atmosphere, to a stirred suspension of 2.3 g of sodium hydride in 20 ml of dimethylformamide (DMF), the reaction temperature being kept at 20°-30° C. by cooling; the mixture is subsequently stirred for 20 hours at room temperature. A solution of 19.5 g of 1-bromo-4-phenoxybutane in 20 ml of DMF is then added dropwise at 5°-10° C., with continued stirring, and whilst cooling with ice. After completion of the addition, stirring is continued for 10 hours at 5°-10° C., after which 200 ml of water are added and the mixture is extracted twice with 100 ml of methylene chloride at a time. The combined organic phases are extracted by shaking with water and dried over magnesium sulfate; removal of the solvent under reduced pressure gives an oil from which, on trituration with 20 ml of diisopropyl ether, 17 g of colorless crystals precipitate; melting point 59°-62° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:7][N:6]=1)=[O:4].[Br:17]Br.C(Cl)Cl.O>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:7]([Br:17])[N:6]=1)=[O:4]
Reactant: COC(=O)c1cnc(N2CCCCC2)cn1
Reactant: BrBr
Solvent: ClCCl
Solvent: O
Solvent: ClC(Cl)Cl
Product: COC(=O)c1cnc(N2CCCCC2)c(Br)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 14.3 %

Procedure:
A mixture of 0.625 g (2.8 mmol) 5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester, 1.12 g (7 mmol) Br2 and 0.142 g (0.48 mmol) FeBr3 in 10 mL CHCl3 was stirred at room temperature for 16 h. The mixture was treated with DCM and water and the organic layer separated and dried with MgSO4. 0.12 g (14%) of the title compound was obtained after evaporation as light yellow crystals which were used without further purification. m/z (ES+): 299.9 (M+H).
Reaction SMILES: [CH:1]([C:3]1[S:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]([CH2:17][CH2:18][CH2:19][CH3:20])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=O.[S:21]=[C:22]([C:24](=[S:26])[NH2:25])[NH2:23]>>[CH2:17]([CH:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:9][O:8][C:7]1[CH:6]=[CH:5][S:4][C:3]=1[C:1]1[S:21][C:22]2[N:23]=[C:1]([C:3]3[S:4][CH:5]=[CH:6][C:7]=3[O:8][CH2:9][CH:10]([CH2:17][CH2:18][CH2:19][CH3:20])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[S:26][C:24]=2[N:25]=1)[CH2:18][CH2:19][CH3:20]
Reactant: NC(=S)C(N)=S
Reactant: CCCCCCC(CCCC)COc1ccsc1C=O
Product: CCCCCCC(CCCC)COc1ccsc1-c1nc2sc(-c3sccc3OCC(CCCC)CCCCCC)nc2s1
Temperature: 200 °C
Reaction time: 5 h
Yield: 29 %

Procedure:
Under a nitrogen atmosphere, 2-formyl-3-(2-butyloctoxy)thiophene (7 g, 23.6 mmol) and rubeanic acid (1.42 g, 11.8 mmol) were added to a flask equipped with Dean-Stark, then heated to 200° C., and stirred for five hours. Then, the reaction mixture was extracted with chloroform, and an organic layer was washed with a saturated saline solution and water. The organic layer was dried with anhydrous magnesium sulfate, and, after filtration, the solvent was distilled off under reduced pressure. By separating and purifying the obtained reaction mixture by silica gel column chromatography in which a mixed solvent of hexane and chloroform was used as a mobile phase, a target substance was obtained as a yellow solid (29% yield). 1H-NMR (400 MHZ, CDCl3, TMS) δ 7.31 (d, J=5.6 Hz, 1 H), 6.88 (d, J=5.6 Hz, 1 H), 4.13 (d, J=4.8 Hz, 2 H), 1.25 (m, 17 H), 0.88 (m, 6 H)
Reaction SMILES: C(=O)(O)[O-].[Na+].[CH3:6][N:7]1[CH2:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[F:14][C:15]1[C:21](F)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1.O>CN(C=O)C>[F:14][C:15]1[C:21]([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([CH3:6])[CH2:8][CH2:9]2)=[CH:20][C:18]([NH2:19])=[C:17]([N+:23]([O-:25])=[O:24])[CH:16]=1
Reactant: Nc1cc(F)c(F)cc1[N+](=O)[O-]
Reactant: CN1CCCNCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN1CCCN(c2cc(N)c([N+](=O)[O-])cc2F)CC1
Temperature: 80 °C
Yield: 90.9 %

Procedure:
36.2 g of sodium bicarbonate and 29.5 g of N-methyl-homopiperazine are added to a solution of 15 g of 4,5-difluoro-2-nitroaniline in 120 mL of anhydrous DMF. The reaction medium is heated at 80° C. using an oil bath for 2H30. The reaction medium is cooled to ambient temperature, and then poured into 400 mL of water. The mixture is cooled using an ice bath and stirred, and precipitation occurs. The precipitate is filtered off through sintered glass. The yellow solid is rinsed with water. The solid is dried in an oven at 40° C. 21 g of 4-fluoro-5-(4-methylperhydro-1,4-diazepin-1-yl)-2-nitrophenylamine are obtained in the form of a yellow solid. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.90 (m, 2H); 2.27 (s, 3H); 2.50 (m masked, 2H); 2.64 (m, 2H); 3.46 (m, 2H); 3.52 (m, 2H); 6.21 (d, J=9.0 Hz, 1H); 7.24 (broad s, 2H); 7.59 (d, J=16.0 Hz, 1H). EI mass spectrum: m/z=268: M+. (base peak)—m/z=253: (M−CH3)+—m/z=198: (M−C4H8N)+—m/z=70: C4H8N+—m/z=57: C3H7N+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]([CH3:31])[CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:19][CH:18]=3)=[O:15])=[CH:7][C:6]=2[CH:32]=1.C1(C)C=CC=CC=1.C(O)C.O.B([O-])([O-])O[C:46]1[CH:51]=[CH:50][C:49]([S:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:31][N:24]([CH2:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:8]2[CH2:9][CH2:10][S:11](=[O:13])(=[O:12])[C:5]3[CH:4]=[CH:3][C:2]([C:46]4[CH:51]=[CH:50][C:49]([S:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])=[CH:48][CH:47]=4)=[CH:32][C:6]=3[CH:7]=2)=[O:15])=[CH:18][CH:19]=1)[CH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1
Reactant: CN(Cc1ccc(NC(=O)C2=Cc3cc(Br)ccc3S(=O)(=O)CC2)cc1)C1CCOCC1
Reactant: CCCCCSc1ccc(OB([O-])[O-])cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCCSc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCS3(=O)=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 43.6 %

Procedure:
To 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (310 mg) was added toluene/ethanol/water (10/1/1, 6.0 ml) and then were added 4-(pentylthio)phenyl borate (182 mg) and potassium carbonate (181 mg), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (34 mg), and the mixture was stirred at 100° C. for 12 hours and cooled to room temperature. The mixture was added to water, and the mixture was extracted with ethyl acetate/THF, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (ethyl acetate/ethanol=3/1) and recrystallized from ethanol to give N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-pentylthiophenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (Compound 78) (161 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[C:11]([CH3:13])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=1.[CH3:23][N:24]([CH3:38])[CH2:25][CH2:26][O:27][C:28]1[CH:29]=[C:30]([CH:32]=[CH:33][C:34]=1[CH:35]([CH3:37])[CH3:36])[NH2:31]>>[CH3:38][N:24]([CH3:23])[CH2:25][CH2:26][O:27][C:28]1[CH:29]=[C:30]([NH:31][C:20]([C:17]2[CH:18]=[CH:19][C:14]([C:3]3[CH:4]=[CH:5][C:6]([C:8]4[N:12]=[C:11]([CH3:13])[O:10][N:9]=4)=[CH:7][C:2]=3[CH3:1])=[CH:15][CH:16]=2)=[O:22])[CH:32]=[CH:33][C:34]=1[CH:35]([CH3:37])[CH3:36]
Reactant: Cc1nc(-c2ccc(-c3ccc(C(=O)O)cc3)c(C)c2)no1
Reactant: CC(C)c1ccc(N)cc1OCCN(C)C
Product: Cc1nc(-c2ccc(-c3ccc(C(=O)Nc4ccc(C(C)C)c(OCCN(C)C)c4)cc3)c(C)c2)no1

Procedure:
The title compound was prepared from 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid (EP0533268A1) and 3-(2-dimethylaminoethoxy)-4-isopropylaniline (D56) using a similar procedure to Example 20 (89%). The freebase was converted to the oxalate salt mp 219°-223° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[S:10][C:9](=[O:11])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C[Si](N[Si](C)(C)C)(C)C.C(O[CH:25]1[O:47][C@H:46]([CH2:48][O:49][C:50](=[O:57])[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C@@H:36]([O:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:26]1[O:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=O)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>CCO.C(Cl)Cl.CC(C)=O.C(Cl)Cl>[NH2:1][C:2]1[C:3]2[S:10][C:9](=[O:11])[N:8]([C@@H:25]3[O:47][C@H:46]([CH2:48][O:49][C:50](=[O:57])[C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[C@@H:36]([O:37][C:38](=[O:45])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C@H:26]3[O:27][C:28](=[O:35])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2[nH]c(=O)sc12
Reactant: CC(=O)OC1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: CCO
Product: Nc1ncnc2c1sc(=O)n2[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Compound 30 (1.22 g, 7.25 mmol) was glycosylated as described for the preparation of 6, requiring HMDS (35 mL), benzoyl-blocked sugar (5: 4.4 g, 8.7 mmol) and TMS-triflate (2.0 mL, 10.3 mmol). After stirring overnight at room temperature, the reaction mixture was refluxed for 2 days and then worked up in the usual manner. The crude mixture was subjected to flash silica gel column chromatography using a gradient of methylene chloride to methylene chloride-acetone 10:1 (v/v) and yielded two products. The first to elute from the column was assumed by 1H NMR to be a bis-glycoside which amounted to 660 mg. The second and major product off the column was obtained as a foam and assigned as the desired 3-ribosyl isomer by UV and 1H NMR: yield 1.04 g (24%): UV λmax (EtOH) 232 nm (ε), 283 (): 1H NMR (DMSO-d6) δ 6.34 (t, 1H, C1 ,H), 7.39-7.98 (m, 17H, benzoyl aromatics and NH2, 8.19 (s, 1H, C5H), and other sugar protons. Anal. Calcd. for C, 60.78: H, 3.95: N, 9.15: S, 5.23. Found: 3.93: N, 8.13: S, 4.85.
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1)(O)=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.[C:43]1([NH2:50])[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH2:49]>C1COCC1.O>[NH2:49][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=1[NH:50][C:1]([CH2:4][CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:14]3[CH:23]=[CH:24][CH:25]=[CH:26][C:13]=3[CH2:12][C:11]=2[CH:27]=1)=[O:2]
Reactant: CCOC(=O)CC1=Cc2ccc(CCCC(=O)O)cc2Cc2ccccc21
Reactant: Nc1ccccc1N
Agent: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CC1=Cc2ccc(CCCC(=O)Nc3ccccc3N)cc2Cc2ccccc21
Temperature: 0 °C
Yield: 88.5 %

Procedure:
A solution of ethyl (±)-3-[3-carboxy-1-propyl]-5H-dibenzo[a,d]cycloheptene-10-acetate (233.7 mg, 0.64 mmole) in dry THF (6.4 mL) was cooled to 0° C. under argon, and 4-methylmorpholine (0.14 mL, 1.28 mmole) was added. The solution was stirred at 0° C. for several min, then isobutyl chloroformate (0.11 mL, 0.83 mmole) was added dropwise. The cloudy reaction was stirred at 0° C. for 0.5 hr, then a solution of 1,2-phenylenediamine (138 mg, 1.28 mmole) in dry THF (0.6 mL) was added rapidly. The reaction was warmed to RT and stirred for 3 hr, then was diluted with H2O (2 mL) and extracted with EtOAc. Drying (MgSO4), concentration, and silica gel chromatography (3:2 EtOAc/hexanes) gave the title compound (257.6 mg, 88%) as a light yellow foam: TLC (3:2 EtOAc/hexanes) Rf 0.40; 1H NMR (250 MHz, CDCl3) δ 6.90-7.23 (m, 10 H), 6.72-6.80 (m, 2 H), 4.33 (d, J=15.0 Hz, 1 H), 4.10-4.25 (m, 2 H), 3.71-3.91 (m, 4 H), 3.32 (dd, J=15.1, 4.0 Hz, 1 H), 2.95 (dd, J=15.1, 9.5 Hz, 1 H), 2.59-2.72 (m, 3 H), 2.54 (dd, J=15.6,9.5 Hz, 1 H), 2.34 (t, J=7.4 Hz, 2 H), 1.98-2.09 (m, 2 H), 1.27 (t, J=7.1 Hz, 3 H); MS (ES) m/e 457 (M+H)+.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[C:24]3[C:23](=[N:25]O)[CH2:22][CH2:21][CH2:20][C:19]=3[NH:18][C:17]=2[CH3:27])=[CH:11][CH:10]=1.[I-].[Na+]>C(O)(=O)C.C1(C)C(C)=CC=CC=1>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([S:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:25][C:5](=[O:7])[CH3:6])[NH:18][C:17]=2[CH3:27])=[CH:13][CH:14]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1[nH]c2c(c1Sc1ccc(Cl)cc1)C(=NO)CCC2
Agent: [I-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: Cc1ccccc1C
Product: CC(=O)Nc1cccc2[nH]c(C)c(Sc3ccc(Cl)cc3)c12
Temperature: 110 °C
Reaction time: 0.75 h

Procedure:
Acetic anhydride (1.1 mL, 11.6 mmol) was added to a stirred slurry of N-[-3-(4-chlorophenylsulfanyl)-2-methyl-4,5,6,7-tetrahydro-1H-indol-4-ylidene]hydroxylamine (3.0 g, 9.8 mmol) in a mixture of acetic acid (15 mL) and xylene (15 mL) at r.t. in reaction flask 1 (mildly exothermic addition) then the mixture was held with stirring for 45 mins. Meanwhile, reaction flask 2 was charged with acetic acid (7.5 mL), xylene (7.5 mL), acetic anhydride (1.1 mL, 11.6 mmol), and sodium iodide (70 mg, 0.47 mmol) and the mixture was heated to 110° C. with stirring. The contents of reaction flask 1 were transferred to reaction is flask 2 in aliquots over a period of 2 h, whilst maintaining the reaction temperature at 110° C. Reaction flask 1 was rinsed with a mixture of xylene (2 mL) and acetic acid (2 mL) which was transferred to reaction flask 2. Subsequently, the reaction mixture was maintained at 110° C. for a further 3 h then allowed to cool to r.t. and held overnight. The reaction mixture was evaporated to dryness in vacuo to leave a dark brown solid residue. This was purified by chromatography on silica gel, eluting with dichloromethane/ethyl acetate to provide the title compound as an off-white solid; 2.74 g (85%); purity 95.6 area % by HPLC; m/z: 331/333 (MH+); 1H-NMR: 11.84 (1H, s), 9.45 (1H, s), 7.45 (1H, d, J=7.7 Hz), 7.29 (2H, d, J=8.3 Hz), 7.17 (1H, d, J=8.0 Hz), 7.04 (1H, t, J=7.9 Hz), 6.98 (2H, d, J=8.2 Hz), 2.40 (3H, s), 1.84 (3H, s).
Reaction SMILES: C1(O)C=CC=CC=1.[OH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2(C3C=CC(O)=CC=3)[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1.CN1CCN(C)C1=O.[OH-].[Na+].Cl>O>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17][CH:16]=2)=[CH:13][CH:14]=1
Reactant: Oc1ccc(C2(c3ccc(O)cc3)CCC(O)CC2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Oc1ccccc1
Solvent: O
Solvent: CN1CCN(C)C1=O
Product: Oc1ccc(C2=CCC(O)CC2)cc1
Yield: 69.3 %

Procedure:
The phenol adducts of 4,4-bis(4-hydroxyphenyl) cyclohexanol obtained as described above were reacted in toto in a manner similar to that described in Example 1 of Japanese Patent Application No. 89890/1987. Namely, the phenol adducts of 4,4-bis(4-hydroxyphenyl)cyclohexanol were added as a whole to a mixture of 100 ml of 1,3-dimethyl-2-imidazolidinone and 1 ml of a 50% aqueous solution of caustic soda. They were then reacted at 200°-220° C. for 3 hours. In the course of the reaction, the reaction system was depressurized after an elapsed time of 0.5 hour so as to draw phenol-containing 1,3-dimethyl-2-imidazolidinone out of the system. After completion of the reaction, the residue in the reaction tank was dissolved in caustic water and then acidified with hydrochloric acid to precipitate crystals. The crystals were collected by filtration, washed with water, dried under reduced pressure and then recrystallized from acetonitrile, thereby obtaining 22.3 g of 4-(4-hydroxyphenyl)-3-cyclohexen-1-ol. Purity: 99.1%. Purity-converted yield: 69.3% based on 4,4-bis(4-hydroxyphenyl)cyclohexanol.
Reaction SMILES: ClC1C=C(Cl)C=C(Cl)C=1[O:10][C:11](=O)[CH2:12][C:13](OC1C(Cl)=CC(Cl)=CC=1Cl)=[O:14].[NH2:26][C:27]([CH:34]([CH3:36])[CH3:35])=[CH:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>BrC1C=CC=CC=1.CCOC(C)=O.CCOCC>[OH:14][C:13]1[C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[C:27]([CH:34]([CH3:35])[CH3:36])[NH:26][C:11](=[O:10])[CH:12]=1
Reactant: CCOC(=O)C=C(N)C(C)C
Reactant: O=C(CC(=O)Oc1c(Cl)cc(Cl)cc1Cl)Oc1c(Cl)cc(Cl)cc1Cl
Solvent: CCOC(C)=O
Solvent: Brc1ccccc1
Solvent: CCOCC
Product: CCOC(=O)c1c(O)cc(=O)[nH]c1C(C)C

Procedure:
Malonic acid bis(2,4,6-trichlorophenyl) ester (1.4 g, 3.05 mmol) and ethyl 3-amino-4-methylpent-2-enoate (480 mg, 3.05 mmol) in bromobenzene (5 mL) was heated at 155° C. for 45 min. The reaction mixture was diluted with EtOAc/Et2O then concentrated in vacuo until a solid crashed out of solution. The solid was collected and rinsed with Et2O and ethyl acetate. The filtrate was concentrated in vacuo, diluted with DCM, and purified by flash chromatography (12-100% EtOAc/isohexane). The fractions containing pure product were concentrated in vacuo and the resulting solid triturated with Et2O and combined with the first batch of solid to give ethyl 4-hydroxy-2-isopropyl-6-oxo-1,6-dihydropyridine-3-carboxylate. MS ESI calc'd. for C11H15NO4 [M+1]+ 226. found 226.
Reaction SMILES: O[CH:2](CCN)C=O.C(OC(=O)C)(=O)C.[C:15]([O:18][CH:19]([CH2:22][CH2:23][NH:24][C:25](=[O:27])[CH3:26])[CH:20]=[O:21])(=[O:17])[CH3:16].[H-].[Na+].CI>N1C=CC=CC=1>[C:15]([O:18][CH:19]([CH2:22][CH2:23][N:24]([CH3:2])[C:25](=[O:27])[CH3:26])[CH:20]=[O:21])(=[O:17])[CH3:16]
Reactant: CC(=O)NCCC(C=O)OC(C)=O
Reactant: NCCC(O)C=O
Agent: [H-]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CI
Solvent: CC(=O)OC(C)=O
Product: CC(=O)OC(C=O)CCN(C)C(C)=O

Procedure:
Treat the diethylacetal of 2-hydroxy-4-aminobutanal with acetic anhydride in pyridine followed by treatment of the resulting diethylacetal of 2-acetoxy-4-acetamidobutanal with sodium hydride and methyl iodide to obtain the diethylacetal of 2-acetoxy-4-(N-methylacetamido)butanal. Remove the acetal protecting group by means of acid to obtain 2-acetoxy-4-(N-methylacetamido)butanal.