Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][C:14]([CH:16]=O)=[CH:15][C:10]=3[N:9]=[N:8]2)=[C:4]([C:20]([F:23])([F:22])[F:21])[CH:3]=1.O1CCCCC1[O:30][N:31]1[C:35](=[O:36])[CH2:34][S:33][C:32]1=[O:37]>>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][C:14](/[CH:16]=[C:34]4/[C:35](=[O:36])[N:31]([OH:30])[C:32](=[O:37])[S:33]/4)=[CH:15][C:10]=3[N:9]=[N:8]2)=[C:4]([C:20]([F:23])([F:21])[F:22])[CH:3]=1
Reactant: O=Cc1ccc2c(c1)nnn2Cc1ccc(Cl)cc1C(F)(F)F
Reactant: O=C1CSC(=O)N1OC1CCCCO1
Product: O=C1S/C(=C\c2ccc3c(c2)nnn3Cc2ccc(Cl)cc2C(F)(F)F)C(=O)N1O

Procedure:
(5Z)-5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-benzotriazol-5-yl}methylidene)-3-hydroxy-1,3-thiazolidine-2,4-dione was prepared from 1-(4-chloro-2-trifluoromethylbenzyl)-1H-benzotriazole-5-carbaldehyde (from Example 258) and 3-(tetrahydropyran-2-yl)oxy-1,3-thiazolidine-2,4-dione (from Example 288) following General Procedure F.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:11][N:12]([CH3:36])[CH:13]([CH2:15][C:16]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:17]([OH:23])[CH2:18][CH2:19][CH2:20][CH:21]=[CH2:22])[CH3:14]>C(Cl)Cl.O>[CH3:36][N:12]([CH3:11])[CH:13]([CH2:15][C:16]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:17](=[O:23])[CH2:18][CH2:19][CH2:20][CH:21]=[CH2:22])[CH3:14]
Reactant: C=CCCCC(O)C(CC(C)N(C)C)(c1ccccc1)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: O
Solvent: ClCCl
Product: C=CCCCC(=O)C(CC(C)N(C)C)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 50.3 %

Procedure:
Anhydrous dimethyl sulfoxide (DMSO, 8.8 ml) was carefully added by syringe to a stirred solution of oxalyl chloride (4.8 ml) in methylene chloride (40 ml), maintained at -50° C. to -60° C. The mixture was then stirred 2 min. A solution of 2-dimethylamino-4,4-diphenyl-9-decene-5-ol (1 g) in methylene chloride (2 ml) was added, and stirring continued for 5 min. The mixture was allowed to warm to room temperature, diluted with water, and washed with sodium bicarbonate solution. Rotary evaporation of the solution gave a crude product which was flash-chromatographed over silica gel. Elution with chloroform/methanol (20:1) yielded 0.5 g of 2-dimethylamino-4,4-diphenyl-9-decene-5-one.
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[N:4]1.Cl.Cl.Cl[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([N:24]3[CH2:29][CH2:28][N:27]([CH2:30][C:31]4[CH:32]=[N:33][N:34]([CH3:37])[C:35]=4[CH3:36])[CH2:26][CH2:25]3)=[N:20][CH:21]=[CH:22][N:23]=2)=[CH:14][CH:13]=1>CN(C=O)C>[CH3:37][N:34]1[C:35]([CH3:36])=[C:31]([CH2:30][N:27]2[CH2:26][CH2:25][N:24]([C:19]3[C:18]([C:15]4[CH:16]=[CH:17][C:12]([CH2:11][N:3]5[CH:7]=[CH:6][CH:5]=[N:4]5)=[CH:13][CH:14]=4)=[N:23][CH:22]=[CH:21][N:20]=3)[CH2:29][CH2:28]2)[CH:32]=[N:33]1
Reactant: Cc1c(CN2CCN(c3nccnc3-c3ccc(CCl)cc3)CC2)cnn1C
Reactant: c1cn[nH]c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1c(CN2CCN(c3nccnc3-c3ccc(Cn4cccn4)cc3)CC2)cnn1C
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 60.5 %

Procedure:
Add sodium hydride (0.172 g of 60% weight suspension in mineral oil; 2.59 mmol) to a solution of pyrazole (0.183 g; 2.69 mmol) in DMF (5 mL). Cool the mixture to 5° C., stir for 30 min., remove the cooling bath, warm to room temperature and stir for 30 min. Add 3′-(4-chloromethyl-phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.253 g; 0.540 mmol) in 6 mL of DMF and stir for 20 hr. at room temperature. Quench with a solution of 10% aq. acetic acid (9 mL), add methanol (minimal volume to achieve a homogeneous solution) and add to a 5 gm SCX column (Varian; pre-rinsed with MeOH). Elute the crude product with 2 M ammonia in methanol (18 mL) and concentrate. Purify via chromatography on silica gel eluting 0-10% methanol/dichlormethane to give 4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3′-(4-pyrazol-1-ylmethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.140 g; 61%). MS (ES+) m/z: 429 (M+H)+. Purify by high pH reverse phase HPLC, and concentrate to give the pure free base. Dissolve the free base in acetonitrile and convert to the hydrochloride salt by adding 1 eq 2 M aq HCl solution. Add water and lyophilize to give the title compound as an off white powder (126 mg). MS (ES): m/z=429 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=O)=O)=[CH:4][CH:3]=1.[C:19]1([NH2:26])[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH2:25]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)=[N:26][C:19]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:25]=2)=[CH:4][CH:3]=1
Reactant: Nc1ccccc1N
Reactant: O=C(C(=O)c1ccc(F)cc1)c1ccc(F)cc1
Solvent: ClC(Cl)Cl
Product: Fc1ccc(-c2nc3ccccc3nc2-c2ccc(F)cc2)cc1
Yield: 99 %

Procedure:
First, 4,4′difluorobenzil of 3.71 g and o-phenylenediamine of 1.71 g are heated and agitated in chloroform solvent of 200 mL for 6 hours. The reaction solution is back to a room temperature, cleaned by 1NHCl and saturated salt solution, and dried by magnesium sulfate. By evapolating the solvent, a ligand HFdpq [2,3-bis(4-fluorophenyl)quinoxaline] is obtained (light yellow powder, yield is 99%). A synthesis scheme and a structural formula of the lignad HFdpq are shown in the following formula (2).
Reaction SMILES: C(OC(=O)N[C@H](C(=O)[NH:13][C@H:14]([B:19]1[O:27][C@H:26]2[C@:21]([CH3:31])([C@H:22]3[CH2:28][C@@H:24]([CH2:25]2)[C:23]3([CH3:30])[CH3:29])[O:20]1)[CH2:15][CH:16]([CH3:18])[CH3:17])C(C)C)(C)(C)C.[C:34]([NH:41][C@H:42]([C:47]([OH:49])=O)[CH2:43][CH:44]([CH3:46])[CH3:45])([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>>[C:37]([O:36][C:34](=[O:35])[NH:41][C@H:42]([C:47](=[O:49])[NH:13][C@H:14]([B:19]1[O:27][C@H:26]2[C@:21]([CH3:31])([C@H:22]3[CH2:28][C@@H:24]([CH2:25]2)[C:23]3([CH3:29])[CH3:30])[O:20]1)[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:43][CH:44]([CH3:45])[CH3:46])([CH3:38])([CH3:39])[CH3:40]
Reactant: CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)C[C@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)B1O[C@@H]2C[C@@H]3C[C@@H](C3(C)C)[C@]2(C)O1
Product: CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)B1O[C@@H]2C[C@@H]3C[C@@H](C3(C)C)[C@]2(C)O1

Procedure:
The title compound is prepared as described for {(S)-2-Methyl-1-[(R)-3-methyl-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-propyl}-carbamic acid tert-butyl ester (example 1 (c)) but using Boc-L-leucine.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][N:4]=[C:5]=[O:6].[S:7]1[C:11]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1.C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[S:7]1[C:11]2[CH:12]=[C:13]([NH:16][C:5]([NH:4][CH2:3][CH2:2][Cl:1])=[O:6])[CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1
Reactant: O=C=NCCCl
Reactant: Nc1ccc2ncsc2c1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=C(NCCCl)Nc1ccc2ncsc2c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 80.1 %

Procedure:
1-Chloro-2-isocyanato-ethane (2.1 g, 19.99 mmol) was added drop wise to a stirred solution of benzothiazol-6-ylamine (2 g, 13.33 mmol) in toluene (80 mL) over a period of 15 minutes at 0° C. The reaction mixture was stirred at room temperature for 18 hours. The reaction was monitored by TLC (50% ethyl acetate in hexane). The reaction mixture was filtered, washed with toluene and dried under reduced pressure to afford 2.73 g (80.2% yield) of 1-benzothiazol-6-yl-3-(2-chloro-ethyl)-urea.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]2[C:19]3[C:14](=[N:15][C:16]([OH:21])=[CH:17][C:18]=3[CH3:20])[NH:13][N:12]=2)=[O:9])[CH2:4][CH2:3]1.[F:22][C:23]([F:34])([F:33])[CH:24]1[CH2:29][CH2:28][N:27]([C:30](Cl)=[O:31])[CH2:26][CH2:25]1>>[CH3:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]2[C:19]3[C:14](=[N:15][C:16]([OH:21])=[CH:17][C:18]=3[CH3:20])[N:13]([C:30]([N:27]3[CH2:26][CH2:25][CH:24]([C:23]([F:33])([F:22])[F:34])[CH2:29][CH2:28]3)=[O:31])[N:12]=2)=[O:9])[CH2:6][CH2:7]1
Reactant: O=C(Cl)N1CCC(C(F)(F)F)CC1
Reactant: Cc1cc(O)nc2[nH]nc(OC(=O)N3CCC(C)CC3)c12
Product: Cc1cc(O)nc2c1c(OC(=O)N1CCC(C)CC1)nn2C(=O)N1CCC(C(F)(F)F)CC1

Procedure:
In analogy to example 12, 99.87 mg (0.344 mmol) of 6-hydroxy-4-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl 4-methylpiperidine-1-carboxylate were reacted with 83.4 mg (0.52 mmol) of 4-trifluoromethylpiperidine-1-carbonyl chloride. Yield: 16 mg (10%), M+H+: 470.20.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@H:16]([OH:20])[CH2:17][CH2:18][CH3:19])[C:11]([O:13]CC)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].S(=O)(=O)(O)[O-].[Na+]>C1COCC1.C(O)C>[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@H:16]([OH:20])[CH2:17][CH2:18][CH3:19])[C:11]([OH:13])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCC[C@@H](O)[C@@H](CCCc1ccccc1)C(=O)OCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCC[C@@H](O)[C@@H](CCCc1ccccc1)C(=O)O
Temperature: 23 °C
Reaction time: 20 h
Yield: 99.9 %

Procedure:
To a solution of ethyl (2R,3R)-2-(3-phenyl-1-propyl)-3-hydroxyhexanoate (1.70 g, 6.12 mmol) in THF-ethanol (2:1, 18 mL) is added 1 N aqueous sodium hydroxide solution (6.7 mL, 6.7 mmol). The solution is stirred at 23° C. for 20 h and is acidified to pH 3 with saturated aqueous sodium bisulfate and is extracted with two 50-mL portions of EtOAc. The combined organic layers are dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide (2R,3R)-2-(3-phenyl-1-propyl)-3-hydroxyhexanoic acid as an oil (1.53 g, 100% yield).
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:16])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.I[C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=1>>[Br:1][C:2]1[C:3]([O:16][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=2)=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:12])([CH3:13])[C:10]=2[CH:11]=1
Reactant: CC1(C)CCC(C)(C)c2cc(Br)c(O)cc21
Reactant: COC(=O)c1ccc(I)cc1
Product: COC(=O)c1ccc(Oc2cc3c(cc2Br)C(C)(C)CCC3(C)C)cc1

Procedure:
In the manner similar to Example 1(a), by the reaction of 1 g (3.5 mmol) of 3-bromo-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthol with 770 mg (2.94 mmol) of methyl 4-iodobenzoate, 700 mg (58%) of the expected methyl ester of melting point 135-6° C. were obtained.
Reaction SMILES: C1(CO[NH:9][C:10]2([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:19][CH2:18][CH2:17][C:16]3[N:15]=[C:14]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:13]=[CH:12][C:11]2=3)C=CC=CC=1.B.O1CCCC1.O>O1CCCC1>[C:22]1([CH2:21][O:20][C:14]2[CH:13]=[CH:12][C:11]3[C:10]([CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)([NH2:9])[CH2:19][CH2:18][CH2:17][C:16]=3[N:15]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc(CONC2(Cc3ccccc3)CCCc3nc(OCc4ccccc4)ccc32)cc1
Agent: B
Solvent: C1CCOC1
Solvent: O
Product: NC1(Cc2ccccc2)CCCc2nc(OCc3ccccc3)ccc21
Temperature: 0 °C
Yield: 62.5 %

Procedure:
5,6,7,8-Tetrahydro-N,2-bis(phenylmethoxy)-5-(phenylmethyl)-5-quinolinamine (40.0 g) in tetrahydrofuran (90 ml) was treated dropwise with borane-tetrahydrofuran complex (1M in tetrahydrofuran, 267 ml) at 0° C. The solution was heated under reflux for 3 hrs, cooled to 0° C. and water (30 ml) was added. The reaction mixture was concentrated in vacuo, 20% potassium hydroxide solution (60 ml) was added, and the mixture was heated under reflux for 8 hours. The mixture was cooled, acidified with conc hydrochloric acid, and washed with diethyl ether. The aqueous phase was basified with 20% potassium hydroxide solution and extracted with dichloromethane. The combined organic layers were washed with brine, dried over potassium carbonate, filtered, and the filtrate was concentrated to afford 19.1 g (37.0%) of product.
Reaction SMILES: C([O:4][C:5]([C:7]1[N:8]([NH:12][CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:9]=[CH:10][CH:11]=1)=[O:6])C=C.Cl.C(ON)C1C=CC=CC=1>ClCCl.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>[CH3:16][CH:15]([CH3:17])[CH2:14][CH2:13][NH:12][N:8]1[CH:9]=[CH:10][CH:11]=[C:7]1[C:5]([OH:6])=[O:4]
Reactant: C=CCOC(=O)c1cccn1NCCC(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: NOCc1ccccc1
Solvent: ClCCl
Product: CC(C)CCNn1cccc1C(=O)O
Temperature: 25 °C
Yield: 81.3 %

Procedure:
To a solution of 1-(3-methyl-butylamino)-1H-pyrrole-2-carboxylic acid allyl ester (Example 1c, 2.8 g, 16 mmol) in dichloromethane (70 mL) was added O-benzylhydroxylamine hydrochloride (2.56 g, 16 mmol). Tetrakis(triphenylphosphine)palladium(0) (3.6 g, 3.2 mmol) was added and the reaction mixture was heated at reflux for 16 h. The crude mixture was allowed to cool to 25° C. The solvent was removed in vacuo and redissolved in ethyl acetate (150 mL) and then washed with 10% aqueous hydrochloric acid solution (3×50 mL) and water (50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (Merck silica gel 60, 40-63 μm, ethyl acetate/hexane, 20-60%) to afford the desired product, 1-(3-methyl-butylamino)-1H-pyrrole-2-carboxylic acid (2.5 g, 13 mmol, 82% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 0.94 (6H, d, J=6.4 Hz), 1.41-1.47 (2H, q, J1=15.2 Hz, J2=6.8 Hz), 1.68 (1H, m), 6.18 (1H, dd, J1=4.0 Hz, J2=2.8 Hz), 6.98-7.02 (2H, m).
Reaction SMILES: [CH2:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([Mg]Br)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](S(C2C=CC=CC=2)(=O)=O)[N:20]=1>C1COCC1>[CH2:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([F:18])[N:20]=2)=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: O=S(=O)(c1ccccc1)c1cccc(F)n1
Reactant: CCCCCCCCOc1ccc([Mg]Br)cc1
Solvent: C1CCOC1
Product: CCCCCCCCOc1ccc(-c2cccc(F)n2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 0.06 mol of 4-octyloxyphenylmagnesium bromide (prepared from 0.06 mol of 4-octyloxybromobenzene and 0.06 mol of 4-octyloxybromobenzene and 0.06 mol of magnesium) and 25 ml of THF is added at 30°-40° C. to a mixture of 0.05 mol of 2A and 15 ml of THF. The mixture is stirred at room temperature for 2 hours and subjected to customary work-up. The unpurified product is processed further in accordance with 2C.
Reaction SMILES: [C:1]([C:4]1[C:5]([CH3:31])=[CH:6][C:7]([O:29][CH3:30])=[C:8]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>C(O)C>[OH:3][CH:1]([C:4]1[C:5]([CH3:31])=[CH:6][C:7]([O:29][CH3:30])=[C:8]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH:9]=1)[CH3:2]
Reactant: COc1cc(OC)cc(N2CCN(C(=O)Nc3cc(C(C)=O)c(C)cc3OC)CC2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COc1cc(OC)cc(N2CCN(C(=O)Nc3cc(C(C)O)c(C)cc3OC)CC2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96 %

Procedure:
1-[(5-Acetyl-2-methoxy-4-methylphenyl)aminocarbonyl]-4-(3,5-dimethoxyphenyl)piperazine(0.2 g, 0.47 mmol) was dissolved in anhydrous ethanol(15 ml), and sodium borohydride(17 mg) was added thereto, and then the resulting mixture was stirred at room temperature for 2 hours, concentrated under the reduced pressure to remove ethanol, and purified by column chromatography(ethylacetate:hexane=1:2) to obtain the titled compound.
Reaction SMILES: Cl.[CH:2]([O:5][C:6]1[CH:7]=[C:8]([C@@H:12]([NH2:14])[CH3:13])[CH:9]=[CH:10][CH:11]=1)([CH3:4])[CH3:3].[Cl:15][C:16]1[CH:36]=[CH:35][C:19]([CH2:20][N:21]2[C:29]3[C:24](=[CH:25][C:26]([C:30](O)=[O:31])=[CH:27][CH:28]=3)[C:23]([CH3:33])=[C:22]2[CH3:34])=[CH:18][C:17]=1[O:37][C@@H:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40]>>[CH:2]([O:5][C:6]1[CH:7]=[C:8]([C@@H:12]([NH:14][C:30]([C:26]2[CH:25]=[C:24]3[C:29](=[CH:28][CH:27]=2)[N:21]([CH2:20][C:19]2[CH:35]=[CH:36][C:16]([Cl:15])=[C:17]([CH:18]=2)[O:37][C@@H:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40])[C:22]([CH3:34])=[C:23]3[CH3:33])=[O:31])[CH3:13])[CH:9]=[CH:10][CH:11]=1)([CH3:4])[CH3:3]
Reactant: COC(=O)[C@H](C)Oc1cc(Cn2c(C)c(C)c3cc(C(=O)O)ccc32)ccc1Cl
Reactant: CC(C)Oc1cccc([C@H](C)N)c1
Agent: Cl
Product: COC(=O)[C@H](C)Oc1cc(Cn2c(C)c(C)c3cc(C(=O)N[C@@H](C)c4cccc(OC(C)C)c4)ccc32)ccc1Cl

Procedure:
The title compound was prepared following the same protocol as described in Step 5, Example 36, using the (S)-1-(3-isopropoxyphenyl)ethanamine hydrochloride instead of the (S)-1-(3-cyclopropylphenyl)ethanamine hydrochloride and (S)-1-(4-chloro-3-((1-methoxy-1-oxopropan-2-yl)oxy)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid instead of the 1-(4-(2-methoxy-2-oxoethoxy)benzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid.
Reaction SMILES: [NH4+].[OH-].[C:3]([O:7][C:8]([N:10]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]#[N:24])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>[Ni].CO>[NH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CC(C)(C)OC(=O)N(CCCCC#N)OCc1ccccc1
Agent: [Ni]
Agent: [NH4+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N(CCCCCN)OCc1ccccc1
Temperature: 0 °C
Reaction time: 3.5 h

Procedure:
N-(5-Aminopentyl)-N-(tert-butoxycarbonyl)-O-benzylhydroxylamine (7) was prepared by adding Raney nickel (W-2 grade, 0.98 g) and concentrated NH4OH (1.6 mL) to a solution of (4) (0.57 g, 1.87 mmol) in methanol (9.5 mL) in a 250 mL Parr bottle. The suspension was cooled to 0° C. and ammonia was gently bubbled in for 10 minutes. Hydrogenation was carried out on a Parr shaker for 3.5 hours at 55-58 psi. The catalyst was filtered off (Celite) and the filtrate was concentrated to give 0.61 g crude product. Column chromatography using 5% concentrated NH4OH/CH3OH yielded 0.48 g of (7) (83% yield): NMR δ 1.25-1.72 (m, 17 H), 2.64 (t, 2 H, J=7), 3.39 (t, 2 H, J=7), 4.78 (s, 2 H), 7.31 (s, 5 H). Anal. calcd. for C17H28N2O3 : C, 66.21; H, 9.15; N, 9.08. Found: C, 66.24, H, 9.18; N, 9.05.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.[CH:15]([N:18]([CH:22]([CH3:24])[CH3:23])[CH2:19][CH2:20][NH2:21])([CH3:17])[CH3:16]>>[CH:15]([N:18]([CH:22]([CH3:24])[CH3:23])[CH2:19][CH2:20][NH:21][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1)([CH3:17])[CH3:16]
Reactant: O=[N+]([O-])c1ccc(Cl)c2ccccc12
Reactant: CC(C)N(CCN)C(C)C
Product: CC(C)N(CCNc1ccc([N+](=O)[O-])c2ccccc12)C(C)C
Yield: 75.7 %

Procedure:
1-Chloro-4-nitronaphthalene and N, N-diisopropylethylenediamine were reacted in the same manner as in Example 1 to obtain the titled compound in a yield of 75.7%.
Reaction SMILES: [Mg].Cl[C:3]1[CH:11]=[CH:10][C:6]([C:7]([CH3:9])=[CH2:8])=[CH:5][CH:4]=1.CI.[C:14]([O:18]OC(=O)C1C=CC=CC=1)([CH3:17])([CH3:16])[CH3:15].C(C1C=CC(C2C=CC(C(C)=C)=CC=2)=CC=1)(C)=C>C(OCC)C.O1CCCC1>[C:14]([O:18][C:3]1[CH:11]=[CH:10][C:6]([C:7]([CH3:9])=[CH2:8])=[CH:5][CH:4]=1)([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OOC(=O)c1ccccc1
Reactant: C=C(C)c1ccc(Cl)cc1
Agent: C=C(C)c1ccc(-c2ccc(C(=C)C)cc2)cc1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CI
Solvent: CCOCC
Product: C=C(C)c1ccc(OC(C)(C)C)cc1
Yield: 69.3 %

Procedure:
The procedure of Example 1 was repeated, except that there was utilized 16.9 grams (0.70 mole) of magnesium metal and 100 grams (0.66 mole) of 4-chloro-α-methylstyrene dissolved in 200 ml. of tetrahydrofuran. The Grignard reaction was started by the addition of a small amount of methyl iodide. After the reaction mixture had been refluxed for 12 hours, there was added at 0° C. in a dropwise manner a solution of 85 grams of t-butylperbenzoate in 300 ml. of ethylether. A crystalline product identified as 4,4'-diisopropenylbiphenyl was isolated from the oil which was recovered by filtering the mixture and washing with methanol. After stripping the methanol, a 69.3% yield of 4-t-butoxy-α-methylstyrene was isolated by fractional distillation as a colorless liquid having a boiling point of 65°-68° C. at 0.03 millimeters.
Reaction SMILES: C1(C)C=CC=CC=1.C(=O)=O.[CH3:11][O:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[C:14]=1C([O-])=O.[Li+].COC1C=CC=C(OC)C=1[Li]>CCCCCC>[CH3:11][O:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:14]=1
Reactant: COc1cccc(OC)c1C(=O)[O-]
Agent: O=C=O
Agent: [Li+]
Agent: [Li]c1c(OC)cccc1OC
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: COc1cccc(OC)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a room temperature solution of 0.24 moles DMR in 55 ml hexane is added dropwise over a 45 minute period a solution of 0.2 mole of the complex solution of Example 1. After stirring 18 hours, the resulting yellow to orange colored mixture of DMPL is slowly drained into a slurry of 80 ml hexane, 70 ml toluene, and approximately 600 g dry ice (large excess of CO2). The carbonylation is continued at approximately -50° C. or 12 hours, then gradually allowed to warm to room temperature. The tan colored mixture of lithium 2,6-dimethoxybenzoate is slowly quenched by pouring into 400 ml of tap water. The resulting mixture is stirred with a magnetic stirrer for 30 minutes. The pale yellow aqueous layer is separated and decolorized with 1 g activated charcoal. The nearly colorless solution is acidified (Ph~1) with 6 N HCl to cause precipitation of DMBA. The crystalline product is filtered and dried. Then the melting point is determined followed by calculation of percent yield based on moles of the complex of Example 1 used. Analysis of the yield of 2,6-dimethoxyphenyllithium resulting from the metalation step is determined by proton NMR. Using this method, a sample of the mixture resulting from the reaction of complex metalating agent and 1,3-dimethoxybenzene is quenched with deuterium oxide. The proton NMR spectrum reveals greater than 95%±5% deuterium incorporation.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](/[CH:20]=[C:21](\[CH3:27])/[C:22]([O:24]CC)=[O:23])[C:6]2[C:11]([C:12]=1[O:13][CH2:14][O:15][CH3:16])=[C:10]([CH2:17][CH2:18][CH3:19])[CH:9]=[CH:8][CH:7]=2.[OH-].[Na+].Cl>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5](/[CH:20]=[C:21](\[CH3:27])/[C:22]([OH:24])=[O:23])[C:6]2[C:11]([C:12]=1[O:13][CH2:14][O:15][CH3:16])=[C:10]([CH2:17][CH2:18][CH3:19])[CH:9]=[CH:8][CH:7]=2
Reactant: CCCc1cccc2c(/C=C(\C)C(=O)OCC)cc(OC)c(OCOC)c12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCc1cccc2c(/C=C(\C)C(=O)O)cc(OC)c(OCOC)c12
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 93.4 %

Procedure:
2.2 g of ethyl (E)-3-(3-methoxy-4-methoxymethoxy-5-propyl-1-naphthyl)-2-methylpropenoate was dissolved in 50 ml of ethanol. A sodium hydroxide aqueous solution (sodium hydroxide 1.4 g/water 50 ml) was added, followed by stirring at 60° C. for 30 minutes. After cooling to room temperature, dilute hydrochloric acid was added to make the reaction mixture acidic, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant crystals were filtered to obtain 1.9 g of the titled compound as pale yellow crystals.