Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[C:3](=[O:8])[NH:2]2.[C:9](=O)([O:15]C(C)(C)C)[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]>O1CCCC1.CN(C)C1C=CN=CC=1>[O:8]=[C:3]1[C@@H:4]2[CH2:7][C@@H:1]([CH:6]=[CH:5]2)[N:2]1[C:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:15]
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Reactant: O=C1NC2C=CC1C2
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C(=O)[C@H]2C=C[C@@H]1C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.5 %

Procedure:
(+)-2-Azabicyclo[2.2.1]hept-5-en-3-one (Chiroscience, Cambridge, England; 54.565 g, 0.500 mole) was dissolved in dry tetrahydrofuran (350 ml). Di-tert-butyl carbonate (Aldrich, 114.87 g, 0.510 mole as 97%) and 4-dimethylaminopyridine (Aldrich, 600 mg) were added to the stirred mixture. The resulting solution was stirred at ambient temperature for 2 hours. Solvent was evaporated under reduced pressure and the residual orange solid was crystallized from toluene-hexanes to give title compound as white crystals (95.72 g, 91%), m.p. 85–86° C.; 1H-NMR (CDCl3) δ 1.50 (s, 9H), 2.24 (app AB q, J=8.4 Hz, 2H), 3.39 (br s, 1H), 4.96 (m, 1H), 6.66 (m, 1H), 6.89 (m, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:20]([NH2:21])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH:23]=[CH:24][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:34](Cl)(=[O:38])[CH:35]([CH3:37])[CH3:36].C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15]2[C:20]([NH:21][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:26])=[O:27])[CH:23]=[CH:24][C:16]=23)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2c(N)cnc3c2ccn3S(=O)(=O)c2ccccc2)CC1
Reactant: CC(C)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)C(=O)Nc1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1NC1CCN(C(=O)OC(C)(C)C)CC1

Procedure:
4-(5-Amino-1-benzenesulfonyl 1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (1.00 g, 2.12 mmol), isobutyryl chloride (225 mg, 2.12 mmol) and triethylamine (590 μL, 4.24 mmol) in DCM (15 mL) were stirred at ambient temperature for 2 hours. The mixture was diluted with DCM, washed with a saturated sodium hydrogen carbonate solution, water and brine, dried through a phase separator and concentrated under vacuum affording 4-(1-benzenesulfonyl-5-isobutyrylamino-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester as a brown residue which was used for the next step without further purification. LCMS (Method B, ESI): RT=3.77 min, m+H=542.36.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)(O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(OCC)(=O)C.ClCCl>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C2(O)CCN(Cc3ccccc3)CC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COc1ccc(C2=CCN(Cc3ccccc3)CC2)cc1

Procedure:
A mixture of 1-benzyl-4-(4-methoxyphenyl)piperidin-4-ol (XIV, Step 1, 8.37 g, 28.1 mmol) and concentrated hydrochloric acid/H2O (1/1, 28 ml) is heated at 76° for 3 min. The resulting slurry is cooled and aqueous sodium hydroxide is added to make the mixture basic. The mixture is extracted several times with dichloromethane and the combined organic extracts are backwashed with saline, dried over magnesium sulfate, concentrated, and the resulting material chromatographed on silica gel eluting with methanol/dichloromethane (4/96). The appropriate fractions are pooled and concentrated to give 1-benzyl-1,2,3,6-tetrahydro-4-(4-methoxyphenyl)pyridine (XVI), MS (m/z) 279; IR (mineral oil) 1515, 738, 1030, 1258, 1250 and 1241 cm-1.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]2[N:25]=[CH:26][C:27]([C:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=1.[N:40]1([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.O>[CH3:14][Si:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][O:10][CH2:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]1[N:5]2[N:25]=[CH:26][C:27]([C:28]3[CH:29]=[N:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:32][CH:33]=3)=[C:4]2[N:3]=[C:2]([N:43]2[CH2:42][CH2:41][N:40]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:45][CH2:44]2)[CH:7]=1
Reactant: C[Si](C)(C)CCOCN(COCC[Si](C)(C)C)c1cc(Cl)nc2c(-c3ccc(-c4ccccc4)nc3)cnn12
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)N1CCN(c2cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3ncc(-c4ccc(-c5ccccc5)nc4)c3n2)CC1
Temperature: 130 °C

Procedure:
A mixture of 5-chloro-3-(6-phenylpyridin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (200 mg, 0.34 mmoL), tert-butyl piperazine-1-carboxylate (224 mg, 1.20 mmoL) and NaHCO3 (116 mg, 1.38 mmoL) in NMP (5 mL) was heated at 130° C. overnight. The mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate: LCMS tR=3.04 Min (5 min run, UV254nm). Mass calculated for, M+ 731.4, observed LC/MS m/z 732.4 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][CH:18]([NH2:22])[CH2:19]2)=[N:14]1.[CH:23](=O)/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[BH4-].[Na+].[OH-].[Na+]>CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.CO>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][CH:18]([NH:22][CH2:23][CH:24]=[CH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:19]2)=[N:14]1
Reactant: O=C/C=C/c1ccccc1
Reactant: COc1ccc2nccc(-n3cc4c(n3)CCC(N)C4)c2n1
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc2nccc(-n3cc4c(n3)CCC(NCC=Cc3ccccc3)C4)c2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 48.6 %

Procedure:
To a suspension of 2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (50 mg, 0.17 mmol) and trans-cinnamaldehyde (20 mg, 0.15 mmol) in Ti(OiPr)4 (0.074 mL, 0.25 mmol) was added CH3OH (1 mL). The suspension was stirred for 3 h at RT. NaBH4 was added (9.0 mg, 0.24 mmol) and the reaction mixture was stirred for another 10 min, followed by the addition of 3 N NaOH (5 mL). The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered, and concentrated. The crude was purified on SiO2 (0-5% CH3OH/CH2Cl2) to give 30 mg (50%) of the title compound as a clear oil. MS (ESI): exact mass calculated for C25H25N5O, 411.21; m/z found, 412.4 [M+H]+. 1H NMR (500 MHz, CDCl3): 9.10 (s, 1H), 8.76 (d, J=5.1, 1H), 8.25 (d, J=9.1, 1H), 8.15 (d, J=5.1, 2H), 7.37 (d, J=7.4, 2H), 7.30 (d, J=7.4, 2H), 7.23-7.20 (m, 1H), 7.18 (d, J=9.1, 1H), 6.57 (d, J=15.9, 1H), 6.34 (dt, J=15.9, 6.4, 1H), 4.10 (s, 3H), 3.55 (d, J=6.4, 2H), 3.15-3.11 (m, 1H), 3.06-3.01 (m, 1H), 2.99 (t, J=5.3, 1H), 2.86-2.80 (m, 1H), 2.53 (q, J=8.5, 1H), 2.17-2.15 (m, 1H), 1.88-1.81 (m, 1H).
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[C:19]([O:23][C:24](=[O:47])[N:25]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([C:38](C)(C)[O:39][SiH2]C(C)(C)C)[CH:32]=1)[CH2:26][CH:27]1[CH2:29][CH2:28]1)([CH3:22])([CH3:21])[CH3:20].CCOC(C)=O>C1COCC1>[C:19]([O:23][C:24](=[O:47])[N:25]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][OH:39])[CH:32]=1)[CH2:26][CH:27]1[CH2:29][CH2:28]1)([CH3:22])([CH3:20])[CH3:21]
Reactant: CC(C)(C)OC(=O)N(Cc1ccc(Cl)c(C(C)(C)O[SiH2]C(C)(C)C)c1)CC1CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N(Cc1ccc(Cl)c(CO)c1)CC1CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 43.8 %

Procedure:
TBAF (1M in THF, 14.0 mL, 14.0 mmol) was added to a sol. of [3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-cyclopropylmethyl-carbamic acid tert-butyl ester (3.08 g, 7.00 mmol) in THF (68 mL) at 0° C. The mixture was stirred for 1 h while warming up to rt. EtOAc was added, and the mixture was washed with aq. sat. NH4Cl and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (CH2Cl2→CH2Cl2/MeOH 9:1) yielded the title compound (1.00 g, 44%). LC-MS: tR=0.99 min; ES+: 326.10.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[S:3]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C:14](O)=[O:15])(=[O:5])=[O:4].S(Cl)([Cl:21])=O>C(Cl)(Cl)Cl>[F:1][C:2]([F:18])([F:17])[S:3]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C:14]([Cl:21])=[O:15])(=[O:5])=[O:4]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)Cc1ccccc1NS(=O)(=O)C(F)(F)F
Solvent: ClC(Cl)Cl
Product: O=C(Cl)Cc1ccccc1NS(=O)(=O)C(F)(F)F
Yield: 71.4 %

Procedure:
To a solution of 10 g of o-(trifluoromethanesulfonamido)phenylacetic acid in 100 ml of chloroform, there were dropwise added 8.4 g of thionyl chloride. After completion of the addition, the resultant mixture was heated and refluxed until the evolution of the gas stopped. Concentration of the reaction mixture gave a solid substance, which was recrystallized from toluene to give 7.6 g of o-(trifluoromethanesulfonamido)phenylacetyl chloride. M.P. 94°-95° C.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]([CH2:12][OH:13])[CH2:9][CH2:8][CH2:7]2.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O>ClCCl>[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]([CH:12]=[O:13])[CH2:9][CH2:8][CH2:7]2
Reactant: Cc1cccc2c1C(CO)CCC2
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: Cc1cccc2c1C(C=O)CCC2
Reaction time: 2 h

Procedure:
(8-Methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-methanol (0.03 g, 0.17 mmol) was dissolved in dichloromethane (0.5 mL). To the solution was then added 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one, also known as Dess-Martin periodinane (0.087 g, 0.20 mmol). The reaction mixture was stirred for 2 hrs then partitioned with an aqueous saturated solution of thiosulfate and dichloromethane. The organic layer was washed with an aqueous saturated solution of thiosulfate, an aqueous saturated solution of sodium bicarbonate, brine, dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield 8-methyl-1,2,3,4-tetrahydro-naphthalene-1-carbaldehyde as a solid.
Reaction SMILES: [CH2:1]([C:4]1([CH3:29])[C:9]2[N:10]([CH2:18][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH2:20])[C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][C:16]=3[C:8]=2[CH2:7][N:6]([CH3:28])[CH2:5]1)C=C>CO.Cl[Pd]Cl>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH:19]2[CH2:20][CH2:1][C:4]3([CH3:29])[CH2:5][N:6]([CH3:28])[CH2:7][C:8]4[C:16]5[CH:15]=[C:14]([CH3:17])[CH:13]=[CH:12][C:11]=5[N:10]([C:9]=43)[CH2:18]2)=[CH:22][CH:23]=1
Reactant: C=CCC1(C)CN(C)Cc2c1n(CC(=C)c1ccc(F)cc1)c1ccc(C)cc21
Agent: Cl[Pd]Cl
Solvent: CO
Product: Cc1ccc2c(c1)c1c3n2CC(c2ccc(F)cc2)CCC3(C)CN(C)C1

Procedure:
To a stirred solution of 4-allyl-5-[2-(4-fluoro-phenyl)-allyl]-2,4,8-trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (50 mg, 0.138 mmol) in MeOH (3 mL) was added PdCl2 (25 mg, 0.14 mmol). Hydrogen gas was purged through the solution for 1 h. The reaction mixture was filtered through Celite bed and the Celite bed was rinsed with MeOH. The filtrate was concentrated under reduced pressure and the residue was purified by reverse HPLC to obtain 6-(4-fluoro-phenyl)-2,3a,10-trimethyl-1,2,3,3a,4,5,6,7-octahydro-2,7a-diaza-cyclohepta[jk]fluorene. 1H NMR (Freebase, CDCl3) δ (ppm): 6.18-7.21 (m, 2H), 6.9-7.1 (m, 4H), 6.8 (m, 1H), 5.0 (d, 2H), 3.96 (d, 2H), 3.1 (d, 2H), 2.62 (m, 1H), 2.56 (s, 3H), 2.38 (s, 3H), 2.3 (m, 2H), 1.65 (m, 2H), 1.42 (s, 3H).
Reaction SMILES: [CH2:1]([OH:8])[C:2]#[C:3][C:4]#[C:5][CH2:6][OH:7].C([O-])([O-])=O.[K+].[K+].[N+:15]([C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1F)([O-:17])=[O:16].[K+].[Br-]>CC(C)=O.O>[CH2:1]([OH:8])[C:2]#[C:3][C:4]#[C:5][CH2:6][OH:7].[N+:15]([C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[O:8][C:1]1[CH:6]=[CH:5][C:4]([N+:15]([O-:17])=[O:16])=[CH:3][C:2]=1[N+:24]([O-:26])=[O:25])([O-:17])=[O:16]
Reactant: O=[N+]([O-])c1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: OCC#CC#CCO
Agent: [Br-]
Solvent: CC(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc(Oc2ccc([N+](=O)[O-])cc2[N+](=O)[O-])c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2,4-hexadiyn-1,6-diol (1.1 g) in acetone (15 ml), K2CO3 (0.5 g) was added. To the stirred solution at room temperature, 2,4-dinitrofluorobenzene (3.8 g) was added gradually and the dark red solution stirred overnight at room temperature. It was poured into excess water, the pale yellow solid filtered off, washed with water and dried. Recrystallization from dioxane ethanol gave short, light pink needles, m.p. 210° C. (4.2 g, 95%). I.R. (KBr): 1592, 1333, 834 (Ar-NO2)cm-1.
Reaction SMILES: FC1C=CC(C[N:7]2C(=O)N(C3SC(C(O)=O)=C(C)N=3)C=N2)=CC=1.[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][C:46]([F:49])([F:48])[F:47])=[CH:41][CH:40]=3)[C:34]2=[O:50])[S:28][C:29]=1[C:30]([OH:32])=O>>[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][C:46]([F:48])([F:47])[F:49])=[CH:41][CH:40]=3)[C:34]2=[O:50])[S:28][C:29]=1[C:30]([NH2:7])=[O:32]
Reactant: Cc1nc(N2CCN(Cc3ccc(OC(F)(F)F)cc3)C2=O)sc1C(=O)O
Reactant: Cc1nc(-n2cnn(Cc3ccc(F)cc3)c2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(Cc3ccc(OC(F)(F)F)cc3)C2=O)sc1C(N)=O

Procedure:
Following the procedure as described in EXAMPLE 1, making variations as required to replace 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methyl-thiazole-5-carboxylic acid with 4-methyl-2-(2-oxo-3-(4-(trifluoromethoxy)benzyl)-imidazolidin-1-yl)thiazole-5-carboxylic acid, the title compound was obtained as a colorless solid: mp 185-187° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.42 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.2 Hz, 2H), 7.29 (br, 2H), 4.44 (s, 2H), 4.01 (t, J=7.3 Hz, 2H), 3.48 (t, J=7.3 Hz, 2H), 2.46 (s, 3H); MS (ES+) m/z 400.7 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[C:8]([O:12][CH3:13])[C:9]=1[O:10][CH3:11])[NH2:6].Br[CH:15]([CH:33]([CH3:35])[CH3:34])[C:16]([O:18]CC1C=CC=C(OC2C=CC=CC=2)C=1)=[O:17]>>[CH3:13][O:12][C:8]1[CH:7]=[C:5]([NH:6][C@H:15]([C:16]([OH:18])=[O:17])[CH:33]([CH3:35])[CH3:34])[CH:4]=[C:3]([O:2][CH3:1])[C:9]=1[O:10][CH3:11]
Reactant: CC(C)C(Br)C(=O)OCc1cccc(Oc2ccccc2)c1
Reactant: COc1cc(N)cc(OC)c1OC
Product: COc1cc(N[C@H](C(=O)O)C(C)C)cc(OC)c1OC

Procedure:
By the above procedure, 3,4,5-trimethoxyaniline is reacted with m-phenoxybenzyl α-bromoisovalerate to yield the m-phenoxybenzyl ester of N-(3,4,5-trimethoxyphenyl)valine. MS m/e 465.2 (M+, 39.0), 182.9 (100).
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[O-2].[Mg+2:22].O(Cl)Cl.[Mg]>>[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Mg+2:22].[C:1]([O-:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: ClOCl
Agent: [Mg+2]
Agent: [Mg]
Product: CCCCCCCCCCCCCCCCCC(=O)[O-]
Temperature: 88.88888888888889 °C

Procedure:
Product from Example 1, amounting to 50 pounds, was placed in a rotary drum dryer and was heated to 192° F. Then 0.41 pounds of commercial grade stearic acid and 0.205 pounds of magnesium oxide powder (93% passing through a 300 mesh U.S. Standard Screen) were added. The stearic acid melted, flowed onto the granules of magnesium oxychloride coated mineral supplement granules and reacted with the magnesium oxide to form a dry, solid magnesium stearate coating on the outside of the granules. The magnesium stearate coating amounted to 1.22% of the total weight of the granules.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]2[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[N:13]=[C:14]([CH3:15])[C:3]=12.[CH2:22]([NH2:25])[CH2:23][CH3:24]>O>[CH3:15][C:14]1[C:3]2[C:4](=[N:5][C:6]3[C:11]([C:2]=2[NH:25][CH2:22][CH2:23][CH3:24])=[CH:10][CH:9]=[CH:8][CH:7]=3)[N:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:13]=1
Reactant: Cc1nn(-c2ccccn2)c2nc3ccccc3c(Cl)c12
Reactant: CCCN
Solvent: O
Product: CCCNc1c2ccccc2nc2c1c(C)nn2-c1ccccn1
Temperature: 100 °C
Reaction time: 6 h
Yield: 71.8 %

Procedure:
A mixture of 4-chloro-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]quinoline (1.47 g, 5.00 mmol) and propylamine (2.96 g, 50.0 mmol) was heated and stirred at 100° C. for 6 hours in a sealed stainless tube. The solution was allowed to cool to room temperature and poured into water, and the organic matter was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue thus obtained was purified by basic silica gel column chromatography (hexane:ethyl acetate=1:1), and the resulting crystals were recrystallized from ethyl acetate/hexane to give the title compound (1.14 g, 72% yield).
Reaction SMILES: [CH2:1]([N:4]([CH2:20][CH2:21][CH3:22])[CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][C:9]([C:17]([O-])=[O:18])=[C:10]([C:14]([O-:16])=O)[CH:11]=2)[CH2:6]1)[CH2:2][CH3:3].[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH2:30])=[CH:27][CH:26]=1.Cl>>[CH2:1]([N:4]([CH2:20][CH2:21][CH3:22])[CH:5]1[CH2:6][C:7]2=[CH:8][C:9]3[C:17](=[O:18])[N:30]([CH2:29][C:28]4[CH:31]=[CH:32][C:25]([O:24][CH3:23])=[CH:26][CH:27]=4)[C:14](=[O:16])[C:10]=3[CH:11]=[C:12]2[CH2:13]1)[CH2:2][CH3:3]
Reactant: COc1ccc(CN)cc1
Reactant: CCCN(CCC)C1Cc2cc(C(=O)[O-])c(C(=O)[O-])cc2C1
Agent: Cl
Product: CCCN(CCC)C1Cc2cc3c(cc2C1)C(=O)N(Cc1ccc(OC)cc1)C3=O

Procedure:
Using procedure 49, 2-(dipropylamino)-2,3-dihydro-1H-indene-5,6-dicarboxylate (92, 0.10 g, 0.28 mmol) was treated with p-methoxybenzylamine (0.05 mL, 0.4 mmol). Purification using silica gel, eluting with 5:1 CH2Cl2 /acetone, afforded an oil that was converted to an HCl salt and recrystallized from EtOAc to give 105 as a white solid (m.p. 255-256° C.).
Reaction SMILES: [H-].[Na+].[C:3]1([CH2:9][C:10]#[N:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.Cl>CS(C)=O.CS(C)=O.CCOCC.O>[C:3]1([C:9]2([C:10]#[N:11])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: N#CCc1ccccc1
Reactant: BrCCCCCBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CS(C)=O
Solvent: O
Product: N#CC1(c2ccccc2)CCCCC1
Reaction time: 2 h
Yield: 65.8 %

Procedure:
To a suspension of NaH (42.7 g, 1067.0 mmol, 60%) in dimethyl sulfoxide (600.0 mL) were added drop-wise a mixture of phenylacetonitrile (50.0 g, 426.8 mmol) and 1,5-dibromopentane (58.1 mL, 426.8 mmol) dissolved in dimethyl sulfoxide:ether (1:1) (200.0 mL) at 0° C. and the reaction mixture was stirred at this temperature for 2 h. After completion of the reaction, water and a 10% HCl solution were added to the mixture and the mixture was extracted with ethyl acetate. The combined organic layer was then washed with water and brine and dried over sodium sulfate and concentrated under reduced pressure to obtain a crude product. This crude product was then purified by normal silica gel column chromatography (using hexane) to get 1-phenyl-cyclohexanecarbonitrile (249) (52.0 g, 65.76%) as a colorless oil.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH2:10].[CH3:11][C:12](OC(C)=O)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:11]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH2:10])[CH3:12]
Reactant: NCCCCCCCCN
Reactant: CC(=O)OC(C)=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCNCCCCCCCCN
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Ten mmole of 1,8 diaminooctane is dissolved in 50 ml of pyridine. Five mmole of Ac2O is added to the solution dropwise at 10° C. The organic solvent is then evaporated. Using column chromatography, N-monoacetoamide-1,8-diaminooctane subsequently is separated out. The N-monoacetoamide-1,8-diaminooctane is dissolved in 25 ml 1,2-dichloroethane. To this solution, 6 mmole of LiAlH4 is added. The solution is then stirred under nitrogen gas at room temperature for 1 day. Subsequently, the solution is diluted with 100 ml of ethyl acetate. The resulting solution is washed with 20 ml of saturated sodium chloride solution. The solution is dried over MgSO4 and evaporated to produce a residue of N-monoethyl-1,8-diaminooctane. The obtained N-monoethyl-1,8-diaminooctane is dissolved in 80 ml of 1,2-dichloroethane containing about 15 mmole of 2-methyl-5-nitro-imidazolyl-1-yl-acetaldehyde. This reaction mixture is stirred for 30 minutes and then acidified with 15 mmole of acetic acid. Eighteen mmole of sodium triacetoxyborohydride is added as a reducing agent and the solution is stirred for 48 hours at room temperature. The resulting mixture is diluted with 80 ml of ethyl acetate, and the mixture solution is washed with 100 ml of saturated aqueous NaHCO3 and 50 ml of water. The organic layer is dried over anhydrous MgSO4, and the solvent is evaporated to leave residual oil which solidified at 4° C. for 2 days. The obtained solid is recrystallized from ethyl acetate/hexane to give N,N,N′-tri[2′-(2-methyl-5-nitro-1-imidazolyl)ethyl]-N′-ethyl-1,8-octanediamine.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4].[Cl:5][C:6]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:7]=1[CH:8]=[CH:9][N+:10]([O-:12])=[O:11]>C1(C)C=CC=CC=1>[Cl:5][C:6]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:7]=1[C@H:8]1[C@H:9]([N+:10]([O-:12])=[O:11])[CH2:4][CH:3]=[CH:2][CH2:1]1
Reactant: O=[N+]([O-])C=Cc1ccc(F)cc1Cl
Reactant: C=CC=C
Solvent: Cc1ccccc1
Product: O=[N+]([O-])[C@@H]1CC=CC[C@H]1c1ccc(F)cc1Cl
Temperature: 110 °C
Reaction time: 72 h

Procedure:
A 10 mL solution of 1:1 1,3-butadiene in toluene stored at −20° C. and 2-chloro-4-fluoro-β-nitrostyrene (2.0 g, 10 mmol) were added to a pressure tube and sealed. The solution was heated to 110° C. and stirred for three days. The reaction mixture was cooled to room temperature, concentrated and the residue was crystallized from hexanes to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.23-7.28 (m, 1H), 7.11-7.25 (m, 3H), 6.94-7.01 (m, 1H), 5.73-5.83 (m, 2H), 5.04-5.13 (m, 1H), 3.99-4.08 (m, 1H), 2.71-2.82 (m, 2H), 2.51-2.61 (m, 1H), 2.15-2.26 (m, 1H).