Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([CH:15]=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=O.[NH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(O[BH-](O[C:33](=O)[CH3:34])OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl.C(O)(=O)C>[N:17]1([CH2:1][C:3]2[CH:8]=[CH:7][C:6]([N:9]3[CH2:14][CH2:13][CH:12]([CH2:15][N:9]4[CH2:34][CH2:33][CH2:4][CH2:5][CH2:6]4)[CH2:11][CH2:10]3)=[CH:5][CH:4]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=Cc1ccc(N2CCC(C=O)CC2)cc1
Reactant: C1CCNCC1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: ClCCl
Product: c1cc(N2CCC(CN3CCCCC3)CC2)ccc1CN1CCCCC1
Reaction time: 16 h

Procedure:
A solution of the product of Example 21 (194.6 mg), piperidine (196 μL), and acetic acid (114 μL) in DCM (5 mL) was treated with sodium triacetoxyborohydride (570 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (10 mL), and the mixture was extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and concentrated under reduced pressure. Chromatography of the residue on silica gel (1-7% 2 M methanolic ammonia/DCM) gave the title compound (193.1 mg).
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([O:9][C:10]([C:12]1([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:11])[CH2:2]2.[Br:24][CH2:25][C:26]([NH:28][C:29]1[CH:33]=[C:32]([CH3:34])[O:31][N:30]=1)=[O:27].C(OCC)(=O)C.CCCC(C)C>C(#N)C>[Br-:24].[CH3:34][C:32]1[O:31][N:30]=[C:29]([NH:28][C:26]([CH2:25][N+:1]23[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]2)[C@@H:3]([O:9][C:10]([C:12]2([C:19]4[S:20][CH:21]=[CH:22][CH:23]=4)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:11])[CH2:2]3)=[O:27])[CH:33]=1
Reactant: O=C(O[C@H]1CN2CCC1CC2)C1(c2cccs2)CCCCCC1
Reactant: Cc1cc(NC(=O)CBr)no1
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CCCC(C)C
Product: Cc1cc(NC(=O)C[N+]23CCC(CC2)[C@@H](OC(=O)C2(c4cccs4)CCCCCC2)C3)no1
Product: [Br-]
Reaction time: 8 h
Yield: 72.8 %

Procedure:
1-Thiophen-2-yl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (Example 5d) (68 mg) and 2-bromo-N-(5-methyl-isoxazol-3-yl)-acetamide (Example 6a) (45 mg) were dissolved in acetonitrile (2 mL) and stirred overnight. Ethyl acetate (10 mL) and isohexane (9 mL) were added and stirred overnight. The resulting crystals were filtered off and washed with ethyl acetate to afford the titled compound (82 mg).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=2[C:14]([F:17])([F:16])[F:15])[CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[CH3:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][C:27]=1[N+:35]([O-])=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:35][C:27]1[CH:28]=[C:29]([CH:33]=[CH:34][C:26]=1[CH3:25])[C:30]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([N:3]2[CH:4]=[CH:5][N:6]=[C:2]2[CH3:1])=[C:8]([C:14]([F:17])([F:15])[F:16])[CH:9]=1)=[O:31]
Reactant: Cc1ccc(C(=O)Cl)cc1[N+](=O)[O-]
Reactant: Cc1nccn1-c1ccc(N)cc1C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(C(=O)Nc2ccc(-n3ccnc3C)c(C(F)(F)F)c2)cc1N
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-(2-methyl-imidazol-1-yl)-3-trifluoromethyl-phenylamine (1.0 g, 4.15 mmol), triethylamine (1.74 mL, 12.5 mmol) in anhydrous CH2Cl2 (60 mL) at 0° C. is added 4-methyl-3-nitro-benzoyl chloride (660 μL, 4.57 mmol) dropwise. After stirring for 2 hours at room temperature, the reaction mixture is poured into 100 mL CH2Cl2 and 50 mL saturated NaHCO3 solution with rapid stirring. After 10 minutes, the mixture is partitioned in a separator funnel and extracted three times with 100 mL CH2Cl2. The organic extracts are washed with brine, and dried over MgSO4. Filtration and concentration under reduced pressure, afforded the desired compound, which is used in the next step without any further purification.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:36]([O:40][C:41](=[O:44])[CH2:42]Br)([CH3:39])([CH3:38])[CH3:37]>O1CCCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([CH:15]([CH2:16][CH2:17][CH2:18][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1)[CH2:42][C:41]([O:40][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:44])=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)CBr
Reactant: O=C(CCCCC1CCCCC1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)CC(CCCC1CCCCC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: -30 °C
Reaction time: 0.75 h
Yield: 76.5 %

Procedure:
A solution of (4S)-4-benzyl-3-(5-cyclohexylpentanoyl)-1,3-oxazolidin-2-one (70.0 g, 204 mmol) in anhydrous tetrahydrofuran (650 ml) was cooled to −70° C. and treated dropwise with sodium hexamethyldisilazide (1M In tetrahydrofuran, 224 ml, 224 mmol) over 45 minutes. The mixture was stirred for a further 45 minutes before being treated with t-butylbromoacetate (31.6 ml, 214 mmol). This mixture was stirred at −70° C. for 30 minutes then warmed to −30° C. and quenched with an aqueous solution of ammonium chloride (20% w/v, 400 ml) and warmed to room temperature. The mixture was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over anhydrous sodium sulphate and the solvent removed under reduced pressure. The solid was recrystallised from hexane to afford the title compound as a white solid (71.4 g).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[O:3][C:4]([F:28])([F:27])[C:5]([F:26])([F:25])[O:6][C:7]([F:24])([F:23])[C:8]([F:22])([F:21])[O:9][C:10]([F:20])([F:19])[CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.BrCCCCCBr.FC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)CO.[CH2:62]([C:70]1[CH:71]=[N:72][C:73]([C:76]2[CH:81]=[CH:80][C:79]([OH:82])=[CH:78][CH:77]=2)=[N:74][CH:75]=1)[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69]>>[CH2:62]([C:70]1[CH:75]=[N:74][C:73]([C:76]2[CH:81]=[CH:80][C:79]([O:82][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][O:12][CH2:11][C:10]([O:9][C:8]([F:21])([F:22])[C:7]([F:23])([F:24])[O:6][C:5]([F:25])([F:26])[C:4]([F:27])([F:28])[O:3][C:2]([F:29])([F:30])[F:1])([F:20])[F:19])=[CH:78][CH:77]=2)=[N:72][CH:71]=1)[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69]
Reactant: CCCCCCCCc1cnc(-c2ccc(O)cc2)nc1
Reactant: FC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)COCCCCCBr
Agent: BrCCCCCBr
Agent: OCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)F
Product: CCCCCCCCc1cnc(-c2ccc(OCCCCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 5-(2-(2-(2-(trifluoromethoxy)tetrafluoroethoxy)tetrafluoroethoxy)-2,2-difluoroethoxy)1-bromopentane (18.3 g, 38.5 mmol; prepared from 1,5-dibromopentane (107 g, 0.7 mol) and 2-(2-(2-(trifluoromethoxy)tetrafluoroethoxy)tetrafluoroethoxy)-2,2-difluoroethanol (125 g, 0.31 mol) essentially as in Example 2) with 5-octyl-2-(4-hydroxyphenyl)pyrimidine (10 g, 35 mmol) to provide product boiling at 200-210° C. at 0.4 torr (yield of 20.8 g).
Reaction SMILES: [CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[N:7]([CH2:16][C:17](O)=[O:18])[N:6]=1)=[O:4].C1C=CC2N(O)N=NC=2C=1.Cl.[CH2:33]([NH:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:34].CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)CCl>[CH3:21][C:2]([CH3:20])([CH3:1])[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[N:7]([CH2:16][C:17]([N:35]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:33][CH3:34])=[O:18])[N:6]=1)=[O:4]
Reactant: CCNCC(C)(C)C
Reactant: COc1ccc2c(C(=O)C(C)(C)C)nn(CC(=O)O)c2c1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCN(CC(C)(C)C)C(=O)Cn1nc(C(=O)C(C)(C)C)c2ccc(OC)cc21
Temperature: 44 °C

Procedure:
Weigh 8.7 mg [3-(2,2-dimethylpropanoyl)-6-methoxy-1H-indazol-1-yl]acetic acid, 7.7 mg HOBt, and 11.5 mg EDC into a 13×100 mm screw cap tube. Add 7.6 mg N-ethyl-2,2-dimethylpropan-1-amine hydrochloride followed by 0.5 mL DMF and 13.6 mg DIEA in that order. The mixture was stirred at 44° C. over night and purified by RP-HPLC using 50-100% MeCN gradient. The pure product fractions were pooled and lyophilized to give the title compound as white solid. LC-MS: 4.04 min. (m/Z=388.3, 410.3).
Reaction SMILES: C([O:3][C:4](=[O:39])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[C:18]([CH2:34][CH2:35][O:36][CH3:37])=[N:19][C:20]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=3)=[N:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH3:38])([CH3:7])[CH3:6])C.[Li+].[OH-]>O1CCCC1.CCOCC>[CH3:37][O:36][CH2:35][CH2:34][C:18]1[C:17]([CH2:16][O:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:5]([CH3:7])([CH3:6])[C:4]([OH:39])=[O:3])=[C:10]([CH3:38])[CH:11]=2)=[C:22]([CH3:23])[N:21]=[C:20]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)[N:19]=1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(OCc2c(C)nc(-c3ccc(C(F)(F)F)cc3)nc2CCOC)cc1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: COCCc1nc(-c2ccc(C(F)(F)F)cc2)nc(C)c1COc1ccc(OC(C)(C)C(=O)O)c(C)c1
Yield: 81.3 %

Procedure:
A solution of 244 mg (0.446 mmol) 2-{4-[4-(2-methoxy-ethyl)-6-methyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester and 1.34 ml 1N LiOH-solution in 2.5 ml tetrahydrofurane was stirred for 2 h at RT. The reaction mixture was taken up in ether and washed with 1N HCl and water. The crude residue was suspended in AcOEt/heptane 1:19. The resulting crystals were filtered off providing 188 mg of pure 2-{4-[4-(2-methoxy-ethyl)-6-methyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-2-methyl-phenoxy}-2-methyl-propionic acid.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]([C@H:22]2[CH2:27][CH2:26][C@H:25]([CH3:28])[CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[S:15][C:16]([S:19][C:20]#N)=[CH:17][N:18]=2)=[O:12])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].SC[C@@H]([C@@H](CS)O)O.ClC[CH2:39][N:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1>>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([N:10]([C@H:22]2[CH2:27][CH2:26][C@H:25]([CH3:28])[CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[S:15][C:16]([S:19][CH2:20][CH2:39][N:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)=[CH:17][N:18]=2)=[O:12])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]
Reactant: ClCCN1CCCC1
Reactant: CC(=O)N1CCC(N(C(=O)Nc2ncc(SC#N)s2)[C@H]2CC[C@H](C)CC2)CC1
Agent: O[C@H](CS)[C@@H](O)CS
Product: CC(=O)N1CCC(N(C(=O)Nc2ncc(SCCN3CCCC3)s2)[C@H]2CC[C@H](C)CC2)CC1

Procedure:
Prepared as described in general procedures (H) and (I) using 1-(1-acetyl-piperidin-4-yl)-1-(trans-4-methyl-cyclohexyl)-3-(5-thiocyanato-thiazol-2-yl)-urea, dithioerythritol and N-(2-chloroethyl)pyrrolidine
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH:11]3[O:15][C:16](=[O:18])[CH:17]=[C:10]23)=[CH:4][CH:3]=1.[C:19]([Li])(C)(C)C.CI>O1CCCC1.CCCCC>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][C:11]3([CH3:19])[O:15][C:16](=[O:18])[CH:17]=[C:10]23)=[CH:4][CH:3]=1
Reactant: [Li]C(C)(C)C
Reactant: O=C1C=C2C(CCCN2Cc2ccc(Cl)nc2)O1
Solvent: CCCCC
Solvent: C1CCOC1
Solvent: CI
Product: CC12CCCN(Cc3ccc(Cl)nc3)C1=CC(=O)O2
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 35 %

Procedure:
43 mg (0.16 mmol) of 4-[(6-chloropyridin-3-yl)methyl]-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one (1-2) are dissolved in 2.5 ml of tetrahydrofuran, the mixture is cooled to −78° C. and 96 μl (0.16 mmol) of a 1.7M solution of tert-butyllithium in pentane are added. After 30 minutes of stirring at −78° C., 15 μl (0.24 mmol) of methyl iodide are added, and the mixture is stirred at −78° C. for a further 30 min, warmed to room temperature and stirred at room temperature for a further 3 hours. Concentration under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm) using the mobile phase ethyl acetate gives 16 mg (35% of theory) of 4-[(6-chloropyridin-3-yl)methyl]-7a-methyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one.
Reaction SMILES: [N:1]1[C:10]2[C:5](=C[CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[K+].[O-:17][Mn](=O)(=O)=O.[K+]>O>[N:1]1[CH:2]=[CH:3][CH:4]=[C:5]2[C:7](=[O:17])[C:8]3[C:9]([C:10]=12)=[CH:11][CH:12]=[CH:13][CH:14]=3
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: c1ccc2c(c1)ccc1cccnc12
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C1c2ccccc2-c2ncccc21
Temperature: 25 °C
Yield: 41.2 %

Procedure:
A solution of benzo[h]quinoline (6 g, 33.5 mmol) and KOH (5.6 g, 100.5 mmol) in water (400 mL) was boiled. A hot solution of KMnO4 (14.8 g, 93.8 mmol) in water (240 mL) was added dropwise over 1 hour to the boiling solution. The mixture was refluxed for another 6 hours and filtered hot. The filtrate was allowed to cool to room temperature. The organic layer was extracted with chloroform and water, dried with anhydrous magnesium sulfate. After solvent removal, the residue was purified by column chromatography on silica (acetone-petroleum ether) to give product 2.5 g (42%) as a yellow solid.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([CH3:11])=[CH:4][N:3]=1.[CH2:12]([O:14][C:15](=[O:27])[CH:16]([CH2:22][CH2:23][CH2:24][C:25]#[N:26])[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:13]>>[C:25]([CH2:24][CH2:23][CH2:22][C:16]([C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([CH3:11])=[CH:4][N:3]=1)([C:15]([O:14][CH2:12][CH3:13])=[O:27])[C:17]([O:19][CH2:20][CH3:21])=[O:18])#[N:26]
Reactant: CCOC(=O)C(CCCC#N)C(=O)OCC
Reactant: Cc1cnc(Cl)c([N+](=O)[O-])c1
Product: CCOC(=O)C(CCCC#N)(C(=O)OCC)c1ncc(C)cc1[N+](=O)[O-]

Procedure:
2-Chloro-5-methyl-3-nitro-pyridine (20 g) was reacted with 2-(3-cyanopropyl)malonic acid diethyl ester under conditions analogous to those in Example 1(a). The reaction mixture was partitioned between water and chloroform, the chloroform extract was dried, treated with charcoal and filtered through a silica bed and then evaporated to a dryness to give 2-[4-cyano-1,1-dicarbethoxybutyl]-3-nitro-5-methylpyridine (18.3 g) as a yellow oil.
Reaction SMILES: [C:1]1([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH:6]=[CH:5][C:4]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]([C:17]2[C:18]([C:26]3[C:27]([C:35]([O:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][O:44][C:45]4[CH:50]=[CH:49][C:48]([C:51]5[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=5)=[CH:47][CH:46]=4)=[O:36])=[CH:28][C:29]([N+:32]([O-])=O)=[CH:30][CH:31]=3)=[CH:19][CH:20]=[C:21]([N+:23]([O-])=O)[CH:22]=2)=[O:16])=[CH:3][CH:2]=1>[Pd].O1CCCC1>[C:1]1([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH:2]=[CH:3][C:4]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]([C:17]2[C:18]([C:26]3[C:27]([C:35]([O:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][O:44][C:45]4[CH:50]=[CH:49][C:48]([C:51]5[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=5)=[CH:47][CH:46]=4)=[O:36])=[CH:28][C:29]([NH2:32])=[CH:30][CH:31]=3)=[CH:19][CH:20]=[C:21]([NH2:23])[CH:22]=2)=[O:16])=[CH:5][CH:6]=1
Reactant: O=C(OCCCCCCOc1ccc(-c2ccccc2)cc1)c1cc([N+](=O)[O-])ccc1-c1ccc([N+](=O)[O-])cc1C(=O)OCCCCCCOc1ccc(-c2ccccc2)cc1
Agent: [Pd]
Solvent: C1CCOC1
Product: Nc1ccc(-c2ccc(N)cc2C(=O)OCCCCCCOc2ccc(-c3ccccc3)cc2)c(C(=O)OCCCCCCOc2ccc(-c3ccccc3)cc2)c1
Reaction time: 24 h

Procedure:
Bis{6-[4-biphenyloxy]hexyl}4,4′-dinitro-2,2′-biphenyldicarboxylate (8) (2.26 g, 2.70 mol), palladium on activated carbon (5%, 0.31 g), and tetrahydrofuran (50 ml) were added to a hydrogenation bottle. The bottle was secured on a Parr hydrogenation apparatus, flushed five times with hydrogen, then pressurized with hydrogen to 56 psi. The pressure was maintained and the vessel was agitated for 24 hours. After the reaction mixture was filtered and about 100 ml of hexanes were added to recrystallize the products directly to afford 1.7 g (80%) of light yellow crystals. mp: 122-124° C. 1H-NMR (CDCl3) δ (ppm) 1.2-1.8 (m, 16H), 3.9 (m, 8H), 6.8-7.6 (m, 24H).
Reaction SMILES: [CH3:1][N:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[C:4]([C:10]#N)[C:3]1=[O:12].S(=O)(=O)(O)[OH:14].[OH2:18]>>[CH3:1][N:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[C:4]([C:10]([OH:14])=[O:18])[C:3]1=[O:12]
Reactant: O
Reactant: Cc1cc(C)n(C)c(=O)c1C#N
Reactant: O=S(=O)(O)O
Product: Cc1cc(C)n(C)c(=O)c1C(=O)O
Yield: 60 %

Procedure:
To a stirred mixture of 1-methyl-3-cyano-4,6-dimethylpyrid-2-one (144 g., 0.89 mole) and 110 ml. of water is slowly added concentrated sulfuric acid (220 ml.) and the solution is heated on a steam bath for 24 hours. The solution is poured into 6 liters of water, cooled, and the resulting precipitate is collected by filtration and dried in a vacuum oven to give 1-methyl-3-carboxy-4.6-dimethylpyrid-2-one, 97 g. (60% yield), mp. 200°-204° C.
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[CH2:21][C:20]2[C:15](=[C:16]([O:28]C)[C:17]([O:26][CH3:27])=[C:18]([O:24][CH3:25])[C:19]=2[O:22]C)[CH2:14]1)(=[O:3])[CH3:2].O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(#N)C.O>[C:1]([O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[CH2:21][C:20]2[C:19](=[O:22])[C:18]([O:24][CH3:25])=[C:17]([O:26][CH3:27])[C:16](=[O:28])[C:15]=2[CH2:14]1)(=[O:3])[CH3:2]
Reactant: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCCCCCOC(C)=O)C2
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: COC1=C(OC)C(=O)C2=C(CC(CCCCCCCCOC(C)=O)C2)C1=O
Reaction time: 0.25 h
Yield: 60.4 %

Procedure:
To a solution of 8-(4,5,6,7-tetramethoxyindan-2-yl)octyl acetate (1.25 g) in acetonitrile (13 ml) was dropwise added a solution of CAN (4.19 g) in water (13 ml) with cooling with ice. After the reaction mixture was stirred for 15 min, water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate=10:1) and then with recrystallization from hexane-diethyl ether to yield the entitled compound (700 mg) as crystals.
Reaction SMILES: [Al](OC(C)C)(OC(C)C)OC(C)C.[CH3:14][C:15](=[CH:18][CH2:19][CH:20]1[CH2:24][CH:23]=[C:22]([CH3:25])[C:21]1([CH3:27])[CH3:26])[CH:16]=[O:17].ClC(Cl)(Cl)C(O)=O.C(O)(C)C>CC(C)=O.C1(C)C=CC=CC=1>[CH3:14][C:15](=[CH:18][CH2:19][CH:20]1[CH2:24][CH:23]=[C:22]([CH3:25])[C:21]1([CH3:27])[CH3:26])[CH2:16][OH:17]
Reactant: CC(C=O)=CCC1CC=C(C)C1(C)C
Agent: CC(C)O[Al](OC(C)C)OC(C)C
Agent: O=C(O)C(Cl)(Cl)Cl
Solvent: CC(C)O
Solvent: CC(C)=O
Solvent: Cc1ccccc1
Product: CC(=CCC1CC=C(C)C1(C)C)CO
Temperature: 25 °C
Reaction time: 6 h
Yield: 81 %

Procedure:
3.07 g (15 mmol) of Al(O-i-Pr)3 and 30 ml of toluene were fed into a 100 ml four-necked round bottom flask under atmosphere of nitrogen, and stirred at room temperature, and then 28.8 g (150 mmol) of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-al, then 0.25 g (1.5 mmol) of trichloroacetic acid, and further 18.0 g (300 mmol) of isopropyl alcohol were added while stirring at room temperature. Reaction was conducted while fraction containing acetone generated at the solution temperature of 80° to 92° C. was distilled off. After 6 hours, the reaction solution was analyzed by GLC, 81% of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was obtained (corresponding to 90% selectivity for conversion of the aldehyde as the starting material).
Reaction SMILES: Cl.[NH2:2][OH:3].[CH3:4][O:5][C:6]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:7]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH3:17])=O>C(O)C.N1C=CC=CC=1>[CH3:4][O:5][C:6]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:7]=1[C:8](=[N:2][OH:3])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH3:17]
Reactant: COc1ccc(C(=O)c2ccccc2OC)c(OC)c1
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: COc1ccc(C(=NO)c2ccccc2OC)c(OC)c1

Procedure:
Hydroxylamine hydrochloride (4.98 g, 71.7 mmol) is added to a solution of 2,2′,4-tri-methoxybenzophenone (J. Org. Chem. 1996, 61, 6326; 6.5 g, 23.9 mmol) in ethanol (50 ml) and pyridine (10 ml). The mixture is heated at reflux for 2 hours and the solvent evaporated. The residue is partitioned between dichloromethane and 2 M aqueous HCl and the organic phase is washed with water, brine, dried (MgSO4) and evaporated to afford the title compound.
Reaction SMILES: [C:1]1(NC(=O)[C@@H]2CCCN2C=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:17](N)=[O:18].[CH:20](N1CCCC1)=O>>[C:1]1([CH:17]([OH:18])[CH3:20])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NC=O
Reactant: O=CN1CCCC1
Reactant: O=CN1CCC[C@H]1C(=O)Nc1ccccc1
Product: CC(O)c1ccccc1
Yield: 99 %

Procedure:
The operation was conducted in the same manner as in Example 1 but using an N-phenyl-1-formyl-(S)-prolineamide which was an amide compound having an oxo group on a carbon atom at the β-position of the nitrogen atom, as a formamide compound, instead of using the 1-formylpyrrolidine and conducting the reaction for 15 hours. As a result, there was obtained 0.121 g of a 1-phenyl-1-ethanol (yield, 99%). Further, this compound was measured for its optical purity to be 32.5% ee (R).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[F:7][C:8]([F:17])([F:16])[C:9]([C:11]1[S:12][CH:13]=[CH:14][N:15]=1)=[O:10]>CS(C)=O>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[C:9]([C:11]1[S:12][CH:13]=[CH:14][N:15]=1)([OH:10])[C:8]([F:17])([F:16])[F:7]
Reactant: Brc1nccs1
Reactant: O=C(c1nccs1)C(F)(F)F
Solvent: CS(C)=O
Product: OC(c1nccs1)(c1nccs1)C(F)(F)F

Procedure:
From 2-bromothiazole and 2-trifluoroacetylthiazole. M.p. 113°-115° C. 13C Nmr (d6 -DMSO) 77.3 (q, J 30Hz), 122.8, 123.0 (q, J 286 Hz), 142.7 and 166.1 ppm. Found: C, 36.25; H, 1.7; N, 10.5. C8H5F3N2OS2 requires C, 36.1; H, 1.9; N, 10.5%.
Reaction SMILES: [N+:1]([C:4]1[C:5]([O:18][CH3:19])=[C:6]([C:10]2[CH:11]=[C:12]([C:15]([OH:17])=[O:16])[O:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O.C([O-])=O.[NH4+]>C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[C:5]([O:18][CH3:19])=[C:6]([C:10]2[CH:11]=[C:12]([C:15]([OH:17])=[O:16])[O:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: COc1c(-c2coc(C(=O)O)c2)cccc1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Product: COc1c(N)cccc1-c1coc(C(=O)O)c1
Yield: 73.3 %

Procedure:
4-(3-nitro-2-methoxy-phenyl)-furan-2-carboxylic acid 22c (500 mg, 1.9 mmol) was dissolved in 15 mL of ethyl acetate followed by addition of 100 mg of palladium on carbon and ammonium formate (429 mg, 7.6 mmol). The reaction mixture was heated to reflux for 3 hours. The mixture was filtered to remove palladium on carbon and concentrated under reduced pressure to obtain the title compound 4-(3-amino-2-methoxy-phenyl)-furan-2-carboxylic acid 22d (325 mg, yield 73.4%) as a yellow oil.
Reaction SMILES: [OH:1]O.O.[OH:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([S:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=3)=[C:12]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[S:11][C:10]=2[CH:28]=1>C(O)(=O)C.C(O)C>[OH:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([S:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=3)=[O:1])=[C:12]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[S:11][C:10]=2[CH:28]=1
Reactant: OO
Reactant: CCOC(=O)c1sc2cc(CO)ccc2c1Sc1cccc(OC)c1
Solvent: CC(=O)O
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1sc2cc(CO)ccc2c1S(=O)c1cccc(OC)c1
Temperature: 100 °C

Procedure:
Hydrogen peroxide in water (0.52 ml of 30% w/v, 4.6 mmol) was added to a solution of ethyl 6-(hydroxymethyl)-3-[(3-methoxyphenyl)sulfanyl]benzo[b]thiophene-2-carboxylate (Preparation 16, 1.73 g, 4.6 mmol) in a mixture of acetic acid (20 ml) and ethanol (10 ml). The mixture was heated to 100° C. for 60 minutes. The solvents were removed by evaporation under reduced pressure, and the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic layer was separated, dried (magnesium sulfate) and concentrated under vacuo, and the residue was flash chromatographed on silica gel using 2% ethanol in dichloromethane as eluant. The title compound was isolated as a foam (1.28 g).