Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[O:11][N:10]=[C:9]([O:12][CH2:13][C:14]([OH:16])=O)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+]([O-])(O)=O.[O:21]([CH2:25][CH2:26][NH2:27])[N+:22]([O-:24])=[O:23].C(OC(C)C)(C)C>>[O:21]([CH2:25][CH2:26][NH:27][C:14](=[O:16])[CH2:13][O:12][C:9]1[CH:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:11][N:10]=1)[N+:22]([O-:24])=[O:23]
Reactant: O=C(O)COc1cc(-c2ccccc2)on1
Reactant: NCCO[N+](=O)[O-]
Solvent: CC(C)OC(C)C
Solvent: O=[N+]([O-])O
Product: O=C(COc1cc(-c2ccccc2)on1)NCCO[N+](=O)[O-]
Yield: 53.2 %

Procedure:
Following a similar treatment to that in Example 2 and using 0.78 g of 5-phenyl-3-isoxazolyloxyacetic acid and 0.60 g of nitroxyethylamine nitrate, 0.58 g of the title compound was obtained as colorless needles (solvent for recrystallization; diisopropyl ether).
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[N:8]1[C:11](=[O:12])[C:10]([CH3:14])([CH3:13])[NH:9]1.[Cl:15][C:16]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:17]=1[CH2:18]Br>>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[N:8]1[C:11](=[O:12])[C:10]([CH3:14])([CH3:13])[N:9]1[CH2:18][C:17]1[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:16]=1[Cl:15]
Reactant: CC1(C)NN(C2CC3CCC2C3)C1=O
Reactant: Fc1ccc(CBr)c(Cl)c1
Product: CC1(C)C(=O)N(C2CC3CCC2C3)N1Cc1ccc(F)cc1Cl

Procedure:
2-(Bicyclo[2.2.1]heptan-2-yl)-4,4-dimethyl-1,2-diazetidin-3-one and 2-chloro-4-fluorobenzyl bromide were used for a similar reaction and treatment as Process 6 of Example 1, and the title compound was obtained as a colorless oil.
Reaction SMILES: [CH:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[C:19]([CH3:20])=[CH:18][C:17]([NH2:21])=[CH:16][C:15]=3[CH3:22])[CH:11]=2)[NH:6][CH:5]=1)([CH3:3])[CH3:2].Br[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26].C([O-])(=O)C.[Na+].O>C(O)C>[CH:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[C:15]([CH3:22])=[CH:16][C:17]([NH:21][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:18][C:19]=3[CH3:20])[CH:11]=2)[NH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: Cc1cc(N)cc(C)c1Oc1ccc2[nH]cc(C(C)C)c2c1
Reactant: CCOC(=O)CBr
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)CNc1cc(C)c(Oc2ccc3[nH]cc(C(C)C)c3c2)c(C)c1

Procedure:
210 mg of 4-[(3-isopropyl-1H-indol-5-yl)oxy]-3,5-dimethylaniline (Example XV) are brought under reflux with 119 mg of ethyl bromoacetate and 117 mg of sodium acetate in 10 ml of ethanol for 24 h. After addition of water, the mixture is extracted with ether, and the organic phase is dried and concentrated in a rotary evaporator. By chromatographic purification (cyclohexane/ethyl acetate), 143 mg (53%) of ethyl N-{4-[(3-isopropyl-1H-indol-5-yl)oxy]-3,5-dimethylphenyl} glycinate are obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[C:21]1([C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1.O.CCOC(C)=O>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][C:27]([OH:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccccc1C(=O)c1ccccc1
Reactant: Cc1ccnc(NC(=O)OC(C)(C)C)c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1ccccc1C(O)(Cc1ccnc(NC(=O)OC(C)(C)C)c1)c1ccccc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 63.7 %

Procedure:
(4-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (300 mg, 1.4 mmol) is dissolved in dry THF (15 mL) and it is cooled down to −78° C. After 1.6 M n-BuLi (4.5 mL, 7.2 mmol) is added at −78° C., the cooling bath is removed and the mixture is stirred at room temperature for 15 min. Then the reaction mixture is cooled down to −78° C. again and phenyl-o-tolyl-methanone (1.3 mL, 7.2 mmol) is added. After the mixture is stirred for 30 min at −78° C., saturated NH4Cl aqueous solution (15 mL) is added and the reaction is warmed up to room temperature. EtOAc (60 mL) is added along with water (50 mL). The mixture is stirred for another 10 min and the aqueous layer is separated, extracted with EtOAc (2×35 ml). The organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) affords 361 mg of the desired product.
Reaction SMILES: [Li]CCCC.[NH:6]1[CH:10]=[CH:9][CH:8]=[CH:7]1.[F:11][C:12]([F:24])([F:23])[C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1>C1COCC1.CCOC(C)=O>[F:24][C:12]([F:11])([F:23])[C:13]1[CH:14]=[CH:15][C:16]([S:19]([N:6]2[CH:10]=[CH:9][CH:8]=[CH:7]2)(=[O:21])=[O:20])=[CH:17][CH:18]=1
Reactant: O=S(=O)(Cl)c1ccc(C(F)(F)F)cc1
Reactant: c1cc[nH]c1
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=S(=O)(c1ccc(C(F)(F)F)cc1)n1cccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.6 %

Procedure:
n-BuLi (56 mL, 89.7 mmol) was added to a solution of 1H-pyrrole (6.02 g, 89.7 mmol) in THF (179 mL) at −78° C. over 10 minutes. 4-(trifluoromethyl)benzene-1-sulfonyl chloride (26.3 g, 107.6 mmol) was dissolved in THF (20 mL) and added to the reaction mixture over 30 minutes. The reaction was stirred for 30 minutes then allowed to warm to room temperature and stirred for a further 18 h. The solution was diluted with EtOAc washed with brine and the organic phase was separated, dried (Na2SO4), filtered and concentrated under vacuum and purified on a silica gel column (eluant hexane/EtOAc 99/1 to 4/1, v/v) to give compound 111 (21.4 g, 77.7 mmol, 87%). MS (ESI) 276.1 (M+H).
Reaction SMILES: [CH2:1]([N:11]1[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[C:13]([C:19]#N)[C:12]1=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[OH2:22].S(=O)(=O)(O)[OH:24]>>[CH2:1]([N:11]1[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[C:13]([C:19]([OH:24])=[O:22])[C:12]1=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: O
Reactant: O=S(=O)(O)O
Reactant: CCCCCCCCCCn1c(C)cc(C)c(C#N)c1=O
Product: CCCCCCCCCCn1c(C)cc(C)c(C(=O)O)c1=O
Temperature: 0 °C

Procedure:
1-(n-decyl)-3-cyano-4,6-dimethylpyrid-2-one (94.6 g., 0.33 mole) is dissolved in concentrated sulfuric acid (300 ml.) and crushed ice (90 g.) is slowly added while maintaining the reaction temperature below 75° C. The reaction mixture is then heated on a steam bath for 23 hours. The cooled reacton mixture is poured onto ice (700 g.) and the reaction mixture is diluted to 2300 ml. with water. The solid is collected by filtration and then triturated with dilute sodium hydroxide and filtered. The alkaline filtrate is acidified to pH 1 with concentrated hydrochloric acid. The resulting solid is collected by filtration and vacuum dried to give 1-(n-decyl)-3-carboxy-4,6-dimethylpyrid-2-one, 62.1 g. mp. 67.5°-72° C. The solid when recrystallized from methanol has a mp. of 74°-76.5° C.
Reaction SMILES: Br.C(O)(=O)C.[C:6]([NH:11][CH:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21]3[CH2:22][CH2:23][C:24](=[O:27])[NH:25][N:26]=3)[CH:18]=2)[CH2:13]1)(=[O:10])[CH2:7][CH2:8][CH3:9].CS(C)=O>C(O)(=O)C>[C:6]([NH:11][CH:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21]3[CH:22]=[CH:23][C:24](=[O:27])[NH:25][N:26]=3)[CH:18]=2)[CH2:13]1)(=[O:10])[CH2:7][CH2:8][CH3:9]
Reactant: CCCC(=O)NC1Cc2ccc(C3=NNC(=O)CC3)cc2C1
Agent: Br
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: CCCC(=O)NC1Cc2ccc(-c3ccc(=O)[nH]n3)cc2C1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 88.1 %

Procedure:
20 m of a 25% hydrogen bromide-acetic acid solution was added to 4.00 g of 2-butyrylamino-5-[4,5-dihydropyridazin-3(2H)-on-6-yl]indane suspended in 45 ml of acetic acid, and then 1.14 ml of dimethyl sulfoxide was added to the mixture. The resulting mixture was stirred at room temperature for 3.5 hours. Hydrogen bromide-acetic acid was removed, and the residue was recrystallized from hydrous ethanol to obtain 3.50 g of 2-butyrylamino-5-[pyridazin-3(2H)-on-6-yl]indane.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].CC(C)=O.[CH2:13]([OH:15])[CH3:14].S(=O)(=O)(O)O.C([O-])(O)=O.[Na+].[C:26]1([CH3:32])[CH:31]=C[CH:29]=[CH:28][CH:27]=1>>[CH2:13]([O:15][C:28]1([CH3:29])[CH2:27][C:26]([CH3:32])([CH3:31])[C:8]2[C:1](=[CH:3][C:4]([OH:5])=[CH:6][CH:7]=2)[O:2]1)[CH3:14]
Reactant: Cc1ccccc1
Reactant: CCO
Reactant: Oc1cccc(O)c1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(C)=O
Product: CCOC1(C)CC(C)(C)c2ccc(O)cc2O1
Temperature: 25 °C
Yield: 21.4 %

Procedure:
50 ml stainless steel autoclave was charged with 2.2 g (20 mmol) of resorcin, 2.32 g (40 mmol) of acetone, 9.2 g (200 mmol) of ethanol, 0.2 g (2 mmol) of conc. sulfuric acid and 10 ml of toluene, then sealed and allowed to react at 100° C. for 4 hours. Then, the reaction mixture was cooled to room temperature, neutralized with saturated NaHCO3, washed with water, and toluene was distilled off under reduced pressure. The residue was purified by column chromatography on silicagel using hexane-ethyl acetate as an eluent to give 1.01 g (21.4%) of 2-ethoxy-7-hydroxy-2,4,4-trimethylchroman as a colorless viscous liquid.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][C:4]([C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[OH:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[Br:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>CC#N>[Br-:23].[CH2:24]([N+:1]12[CH2:6][CH2:5][C:4]([C:9]([OH:10])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)([CH2:3][CH2:2]1)[CH2:7][CH2:8]2)[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: OC(c1ccccc1)(c1ccccc1)C12CCN(CC1)CC2
Reactant: CCCCCCBr
Solvent: CC#N
Product: CCCCCC[N+]12CCC(C(O)(c3ccccc3)c3ccccc3)(CC1)CC2
Product: [Br-]
Yield: 72.1 %

Procedure:
Following the general procedure outlined in Example 3, 1-azabicyclo[2.2.2]oct -4-yl(diphenyl)methanol (0.0498 g, 0.170 mmol) and 1-bromohexane (0.040 mL, 0.285 mmol) in 2 CH3CN/3CHCl3 (4.0 mL) were reacted to give the desired product (0.0562 g, 73.0%). ELMS m/z 378(M+) Rt (2.09 min).
Reaction SMILES: C([N:8]1[CH2:25][CH2:24][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH2:21]C[C:19](=[O:22])[C:18]=3[CH3:23])[CH2:13][CH2:12]2)[CH:10]([OH:26])[CH2:9]1)C1C=CC=CC=1.C(O[C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(C)(C)C.[OH:39]CC1(OC[C@@H](O)[C@@H](O)[C@H]1O)O>CO.[Pd]>[OH:26][CH:10]1[CH2:9][N:8]([C:32]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:38])[CH2:25][CH2:24][C:11]21[C:15](=[O:16])[N:14]([C:17]1[CH2:21][O:39][C:19](=[O:22])[C:18]=1[CH3:23])[CH2:13][CH2:12]2
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Reactant: OCC1(O)OC[C@@H](O)[C@@H](O)[C@H]1O
Reactant: CC1=C(N2CCC3(CCN(Cc4ccccc4)CC3O)C2=O)CCC1=O
Agent: [Pd]
Solvent: CO
Product: CC1=C(N2CCC3(CCN(C(=O)OC(C)(C)C)CC3O)C2=O)COC1=O

Procedure:
To a solution of 8-benzyl-6-hydroxy-2-(2-methyl-3-oxocyclopent-1-en-1-yl)-2,8-diazaspiro[4.5]decan-1-one (CIS) (10 g, 28.2 mmol) and di-tert-butylcarbonate (7.21 ml, 31.0 mmol) in methanol (50 ml) was added palladium on carbon (1.501 g, 1.411 mmol), and the resulting mixture was subjected to hydrogenation at 45 Psi at rt over the weekend. The suspension was filtered through CELITE® under nitrogen, the filtrate was concentrated and the residue was purified on silica gel using ethyl acetatehexane as eluting solvents to give the title compound. LC/MS: (M+1)+: 367.17.
Reaction SMILES: C([C:5]1[CH:10]=[CH:9][CH:8]=[C:7](C(C)(C)C)[C:6]=1[OH:15])(C)(C)C.[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>S(=O)(=O)(O)O>[CH:10]1[C:9]([C:19]2[CH:20]=[CH:21][C:16]([OH:22])=[CH:17][CH:18]=2)=[CH:8][CH:7]=[C:6]([OH:15])[CH:5]=1
Reactant: Oc1ccccc1
Reactant: CC(C)(C)c1cccc(C(C)(C)C)c1O
Agent: O=S(=O)(O)O
Product: Oc1ccc(-c2ccc(O)cc2)cc1

Procedure:
A starting material which was a mixture of 3,3',5,5'-tetra-t-butyl-4,4'-diphenoquinone (1.0 g) and 2,6-di-t-butylphenol (1.0 g) was subjected to reaction at 180° C. for 1 hour in a nitrogen gas atmosphere using 10 ml of phenol as a solvent and 0.05 g of sulfuric acid as a catalyst. p,p'-biphenol was produced in an amount of 0.49 g (yield, 54.0%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:35])[C:4]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:6]([C:7]([NH:9][CH:10]2[CH2:15][CH2:14][N:13](CC3C=C(OCC)C(F)=C(OCC)C=3)[CH2:12][CH2:11]2)=[O:8])[CH:5]=1.[CH2:36]([O:38][C:39]1[CH:44]=[C:43]([CH:45]=O)[CH:42]=[C:41]([O:47][CH2:48][CH3:49])[C:40]=1[C:50]1[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=1)[CH3:37].C([BH3-])#N.[Na+].C(N(C(C)C)C(C)C)C>C(O)C.C(O)(=O)C>[CH3:1][O:2][C:3](=[O:35])[C:4]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:6]([C:7]([NH:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:45][C:43]3[CH:44]=[C:39]([O:38][CH2:36][CH3:37])[C:40]([C:50]4[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=4)=[C:41]([O:47][CH2:48][CH3:49])[CH:42]=3)[CH2:14][CH2:15]2)=[O:8])[CH:5]=1
Reactant: CCOc1cc(CN2CCC(NC(=O)c3cc(OC)cc(C(=O)OC)c3)CC2)cc(OCC)c1F
Reactant: CCOc1cc(C=O)cc(OCC)c1-c1ccc(F)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1cc(CN2CCC(NC(=O)c3cc(OC)cc(C(=O)OC)c3)CC2)cc(OCC)c1-c1ccc(F)cc1

Procedure:
In analogy to the procedure described in example 50k), 5-methoxy-N-piperidin-4-yl-isophthalamic acid methyl ester (example 143) was reacted with 2,6-diethoxy-4′-fluoro-biphenyl-4-carbaldehyde (example 102), sodium cyanoborohydride, N-ethyl-diisopropylamine and acetic acid in ethanol at 50° C. to yield the title compound as off-white solid. MS: 565.3 (MH+).
Reaction SMILES: [NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15]OS(C)(=O)=O)=[CH:10][CH:9]=2)[C:6](=[O:21])[CH:5]=[CH:4][C:3]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1.[CH:31]1([O:36][C:37](=[O:44])[C@H:38]([CH2:40][CH:41]([CH3:43])[CH3:42])[NH2:39])[CH2:35][CH2:34][CH2:33][CH2:32]1>>[NH2:1][C:2]1[N:7]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][NH:39][C@H:38]([C:37]([O:36][CH:31]3[CH2:32][CH2:33][CH2:34][CH2:35]3)=[O:44])[CH2:40][CH:41]([CH3:43])[CH3:42])=[CH:12][CH:13]=2)[C:6](=[O:21])[CH:5]=[CH:4][C:3]=1[C:22]([C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)=[O:30]
Reactant: CC(C)C[C@H](N)C(=O)OC1CCCC1
Reactant: CS(=O)(=O)OCCc1ccc(-n2c(N)c(C(=O)c3ccc(F)cc3)ccc2=O)cc1
Product: CC(C)C[C@H](NCCc1ccc(-n2c(N)c(C(=O)c3ccc(F)cc3)ccc2=O)cc1)C(=O)OC1CCCC1

Procedure:
From Intermediate 4J and L-Leucine cyclopentyl ester (Intermediate 8). LC/MS: m/z 534 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ: 8.47 (1H, d, J=7.7 Hz), 7.56 (2H, m), 7.45 (1H, d, J=9.6 Hz), 7.38-7.24 (4H, m), 7.15 (2H, m), 5.69 (1H, d, J=9.8 Hz), 5.09 (1H, t, J=5.3 Hz), 4.63 (2H, m), 4.31 (1H, m), 1.84-1.79 (2H, m), 1.66-1.53 (9H, m), 0.92-0.86 (6H, m).
Reaction SMILES: C(N(CC)CC)C.[CH:8]1[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11]([S:17](Cl)(=[O:19])=[O:18])=[CH:10][CH:9]=1.Cl.[NH2:22][C@H:23]([C@H:26]1[O:30][C:29](=[O:31])[C@H:28]([CH:32]([CH3:34])[CH3:33])[CH2:27]1)[CH2:24][OH:25].O1CCCC1>O>[OH:25][CH2:24][C@H:23]([NH:22][S:17]([C:11]1[CH:10]=[CH:9][CH:8]=[CH:13][C:12]=1[N+:14]([O-:16])=[O:15])(=[O:19])=[O:18])[C@@H:26]1[CH2:27][C@@H:28]([CH:32]([CH3:34])[CH3:33])[C:29](=[O:31])[O:30]1
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: CC(C)[C@@H]1C[C@@H]([C@@H](N)CO)OC1=O
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)[C@@H]1C[C@@H]([C@H](CO)NS(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Reaction time: 12 h
Yield: 62 %

Procedure:
14 ml of triethylamine (101 mmol) and 11.12 g of O-nitrobenzenesulfonyl chloride (50.1 mmol) were added to a solution of 8.50 g of (3S,5S)-5-[(S)-1-amino-2-hydroxyethyl]-3-isopropyldihydrofuran-2-one hydrochloride obtained in the above reaction (33.5 mmol) in a mixed solvent of tetrahydrofuran (170 ml) and water (17 ml) at room temperature, and the mixture was stirred at the same temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, followed by extraction with ethyl acetate. Then, the organic layer was washed with water, a saturated sodium bicarbonate aqueous solution and brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:ethyl acetate). Further, 110 ml of diisopropyl ether and 11 ml of ethyl acetate were added, and the precipitated solid was collected by filtration to obtain 8.78 g of the title compound (total yield over two steps: 70%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:13]O)=[N:4][N:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.S(Cl)([Cl:17])=O.O.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[Cl:17][CH2:13][C:3]1[C:2]([CH3:1])=[N:6][N:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]=1
Reactant: Cc1nn(-c2ccccc2)nc1CO
Reactant: O=S(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: Cc1nn(-c2ccccc2)nc1CCl
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.8 %

Procedure:
5.0 g of (5-methyl-2-phenyl-1,2,3-triazol4-yl)methan-1-ol was dissolved in 35 ml of dichloromethane, then 6.3 g of thionyl chloride was added dropwise thereto under cooling with ice. After stirring for 1 hour at room temperature, 100 ml of water was added. The resulting solution was made alkaline with 8 g of potassium carbonate, then extracted with chloroform. The organic phase was washed with water and a saturated salt solution, then dried over anhydrous sodium sulfate. After the solvent was distilled off, 5.2 g of the aimed compound was obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][CH2:5][C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[NH:8][C:7]=1[CH:15]=O.[CH3:18][NH:19][S:20]([C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[CH2:26]2)(=[O:22])=[O:21].N1CCCCC1>C(O)C>[CH3:18][NH:19][S:20]([C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])/[C:26]/2=[CH:15]\[C:7]1[NH:8][C:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=2[C:6]=1[CH2:5][CH2:4][CH2:3][N:2]([CH3:17])[CH3:1])(=[O:22])=[O:21]
Reactant: CNS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Reactant: CN(C)CCCc1c(C=O)[nH]c2c1CCCC2
Solvent: CCO
Solvent: C1CCNCC1
Product: CNS(=O)(=O)c1ccc2c(c1)/C(=C/c1[nH]c3c(c1CCCN(C)C)CCCC3)C(=O)N2
Yield: 70 %

Procedure:
3-(3-Dimethylaminopropyl)-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (71 mg, 0.3 mmol), 5-methylaminosulfonyloxindole (68 mg, 0.3 mmol) and piperidine (0.03 ml) in 1 ml of ethanol was stirred at 60° C. for over night. The mixture was cooled and the solids collected by vacuum filtration and washed with ethanol to give (93 mg, 70% yield) of 3-[1-[3-(3-dimethylaminopropyl)-4,5,6,7-tetrahydro-1H-indol-2-yl]-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid methylamide.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[CH2:14](I)[CH2:15][CH3:16]>>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][N:11]2[CH2:14][CH2:15][CH3:16])=[CH:7][CH:6]=1)=[O:4]
Reactant: CCCI
Reactant: COC(=O)c1ccc2cc[nH]c2c1
Product: CCCn1ccc2ccc(C(=O)OC)cc21

Procedure:
This compound was prepared from methyl-6-indolecarboxylate and propyliodide by the method described in Example 10, part i. The reaction mixture was worked up by removal of the dimethylformamide in vacuo and the residue partitioned between diethyl ether and water. The organic phase was further washed with water and brine, dried and evaporated. The resulting oil was purified by chromatography on flash silica eluting with petroleum spirit 40°-60° C.-diethyl ether (9:1) to give the product as a colourless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:24][C:25]#N)[CH:12]=[CH:13][C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH3:23])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:27].[K+].Cl.[OH2:30]>C(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:24][C:25]([OH:30])=[O:27])[CH:12]=[CH:13][C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH3:23])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCc1ccc(Cc2ccc(CC#N)cc2OCc2ccccc2)cc1
Reactant: [OH-]
Reactant: O
Agent: Cl
Agent: [K+]
Solvent: CCO
Product: CCc1ccc(Cc2ccc(CC(=O)O)cc2OCc2ccccc2)cc1

Procedure:
To a mixture of [3-benzyloxy-4-(4-ethylbenzyl)-phenyl]acetonitrile (0.41 g) in ethanol (5 mL) and water (10 mL) was added potassium hydroxide (0.68 g), and the mixture was heated under reflux for 4 hours. The reaction mixture was acidified by adding 2 mol/L aqueous hydrochloric acid solution, and the mixture was extracted with diethyl ether. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give [3-benzyloxy-4-(4-ethylbenzyl)phenyl]acetic acid (0.41 g). To a solution of the obtained [3-benzyloxy-4-(4-ethylbenzyl)-phenyl]acetic acid (0.41 g) in tetrahydrofuran (10 mL) were added pyridine (0.19 mL), di-tert-butyl dicarbonate (0.50 g) and ammonium hydrogen carbonate (0.18 g), and the mixture was stirred at room temperature for 18 hours. To the reaction mixture was added 1 mol/L aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1) to give 2-[3-benzyloxy-4-(4-ethylbenzyl)phenyl]acetamide (0.38 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C([O:40][C:41](=[O:62])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[C:45]([C:51]2[CH:52]=[CH:53][C:54]([F:61])=[C:55]3[C:60]=2[CH2:59][NH:58][CH2:57][CH2:56]3)[CH:44]=1)C.C(N(CC)CC)C>C(Cl)Cl>[F:61][C:54]1[CH:53]=[CH:52][C:51]([C:45]2[CH:44]=[C:43]([CH2:42][C:41]([OH:62])=[O:40])[CH:48]=[CH:47][C:46]=2[O:49][CH3:50])=[C:60]2[C:55]=1[CH2:56][CH2:57][N:58]([C:10](=[O:12])[CH2:9][C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)([CH3:14])[CH3:13])[CH2:59]2
Reactant: CCOC(=O)Cc1ccc(OC)c(-c2ccc(F)c3c2CNCC3)c1
Reactant: CC(C)(CC(=O)O)c1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COc1ccc(CC(=O)O)cc1-c1ccc(F)c2c1CN(C(=O)CC(C)(C)c1ccc(F)cc1)CC2
Temperature: 25 °C
Reaction time: 0.03 h

Procedure:
To a solution of 3-(4-fluoro-phenyl)-3-methyl-butyric acid (20 mg, 0.1 mmol, 1.0 eq.) in DCM (1 mL), 1-hydroxybenzotriazole hydrate (HOBt) (14 mg, 0.1 mmol, 1.0 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol, 1.0 eq.) were added in sequence. The resulting solution was stirred at r.t. for 2 minutes. Then a solution of [3-(5-fluoro-1,2,3,4-tetrahydro-isoquinolin-8-yl)-4-methoxy-phenyl]-acetic acid ethyl ester (34 mg, 0.1 mmol, 1.0 eq.) and triethylamine (42 μL, 0.3 mmol, 3.0 eq.) in DCM (1 mL) was added and the resulting mixture was stirred at r.t. for 18 hours. The mixture was concentrated in vacuo. The residue was dissolved in DMF (0.8 mL). 1M aq. NaOH (1 mL) was added. The mixture was stirred at r.t. for 3 hours. The solution was carefully neutralized with formic acid (0.5 mL), and purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound as a white solid.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].Cl.[NH2:14][OH:15].[OH-].[K+].Cl>C(O)C.O>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6](=[N:14][OH:15])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCC(=O)CCCCC
Reactant: NO
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCC(CCCCC)=NO
Temperature: 0 °C
Yield: 100.2 %

Procedure:
To a solution of 5.11 g of 6-undecanone in 20 ml of ethanol were successively added a solution of 3.47 g of hydroxylamine hydrochloride in 6 ml of water and a solution of 4.77 g of potassium hydroxide in 6 ml of water. The resulting mixture was heated under reflux for 3 hours. The reaction mixture was then poured into 150 ml of ice-containing water. The resulting aqueous mixture was made acidic by addition of 2 N hydrochloric acid, and extracted with benzene. The organic layer was washed with saturated aqueous sodium chloride and evaporated under reduced pressure to remove the solvent. There was obtained 5.57 g (corresponding to theoretical amount) of 6-undecanone oxime as a pale yellow solid,