Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([N+:9]([O-])=O)[C:3]=1[CH3:12].[H][H]>CO.[Pt]>[NH2:9][C:4]1[C:3]([CH3:12])=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=1[OH:8]
Reactant: [H][H]
Reactant: Cc1c(Br)ccc(O)c1[N+](=O)[O-]
Agent: [Pt]
Solvent: CO
Product: Cc1c(Br)ccc(O)c1N
Yield: 98.8 %

Procedure:
4-Bromo-3-methyl-2-nitrophenol (10 g, 43.1 mmol) was dissolved in methanol (254 ml), purged with nitrogen and loaded with Pt/C (1.013 g, 10.13 mmol). The reaction was stirred under 60 psi of hydrogen for 5 hours. When complete, the reaction was filtered carefully on Celite™. The top was covered by more Celite™, flushed with ethyl acetate and dichloromethane and allowed to dry a bit before adding more. The organics were concentrated and 2-amino-4-bromo-3-methylphenol (8.6 g, 99%) was isolated as a brown solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.67 (d, J=9.0 Hz, 1 H), 6.93 (d, J=9.0 Hz, 1 H), 2.63 (s, 3 H); LC/MS (m/z) ES+=202 (M+1).
Reaction SMILES: [Na+:1].[C:2](/[C:6](=[CH:12]/[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)/[CH2:7][S:8]([O-:11])(=[O:10])=[O:9])([O:4][CH3:5])=[O:3].[H][H]>[Ni].CO.O>[Na+:1].[C:2]([CH:6]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:7][S:8]([O-:11])(=[O:10])=[O:9])([O:4][CH3:5])=[O:3]
Reactant: [H][H]
Reactant: COC(=O)/C(=C/c1ccccc1)CS(=O)(=O)[O-]
Agent: [Ni]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COC(=O)C(Cc1ccccc1)CS(=O)(=O)[O-]
Reaction time: 24 h
Yield: 88 %

Procedure:
To the 8 L of 1:1 methanol/water mixture containing the resultant compound from Example 1C was added 60 g of W-24 raney nickel. The resulting suspension was pressurized under 50 psi of hydrogen and was allowed to shake on a Parr shaker for 24 h, at which time an additional 20 g of raney nickel catalyst was added. After 6 h under 50 psi of hydrogen, the catalyst was removed by filtration and the solution was concentrated to dryness. To the dry white solid was added ethyl acetate (6 L) and heptane (4 L) and the solution was vigorously stirred with a mechanical stirrer overnight. The white suspension was removed by filtration yielding 530 g (88%) of the desired product as an amorphous powder that was contaminated with approximately one equivalent of NaBr. The compound was used without any additional purification: IR (KBr) 1740, 1215, 1050 cm-1. 1H NMR (DMSO D-6) δ 2.48-2.54 (m, 1H), 2.74-2.87 (m, 2H), 2.91-3.04 (m, 2H), 3.48 (s, 3H), 7.12-7.32 (m, 5H), 13C NMR (75 MHz, D2O/DMSO D-6) δ 38.18, 44.80, 52.67, 52.82, 127.42, 129.13, 129.34, 138.14, 176.84.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:9]([S:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][CH:7]=[CH:6][C:5]=12.[CH2:17]1N2CN3CN(C2)CN1C3.C(OCC)(=O)C>C(O)(=O)C>[N:1]1[CH:2]=[C:3]2[N:4]3[C:9](=[CH:8][CH:7]=[CH:6][C:5]=13)[S:10][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:17]2
Reactant: C1N2CN3CN1CN(C2)C3
Reactant: CCOC(=O)CSc1cccc2nccn12
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CCOC(=O)C1=Cc2cnc3cccc(n23)S1
Temperature: 25 °C
Reaction time: 1 h
Yield: 78.1 %

Procedure:
To a solution of ethyl (imidazo[1,2-a]pyridin-5-ylthio)acetate (11.8 g) in acetic acid (120 ml) was added hexamethylenetetramine (14.0 g) and the mixture was reacted at 90° C. for 10 hours. After this reaction mixture was allowed to cool, ethyl acetate (360 ml) was added and the mixture was washed with water. The organic layer was neutralized with 30% aqueous solution of sodium hydroxide under ice-cooling and washed again with water. The organic layer was concentrated and n-hexane (100 ml) was added to the crystalline residue, followed by 1 hour of stirring at room temperature. The crystals were collected by filtration and dried to provide the title compound (9.6 g, 78%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[CH2:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4].[CH3:23][Al](C)C.C[Zn]C.CCCCCCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([OH:20])([CH3:23])[CH2:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=[O:4]
Reactant: C[Al](C)C
Reactant: COC(=O)c1cncn1C1c2ccccc2C(=O)CC1(C)C
Agent: C[Zn]C
Solvent: Cc1ccccc1
Solvent: CCCCCCC
Product: COC(=O)c1cncn1C1c2ccccc2C(C)(O)CC1(C)C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a solution of 3-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester, which can be prepared as described in Example 13, (985 mg, 3.31 mmol) in toluene (35 mL) at −78° C. is added a 2.0 M solution of trimethyl aluminum in toluene (3.3 mL, 6.6 mmol) followed by a 1.0 M solution of dimethyl zinc in heptane (6.6 mL, 6.6 mmol). The reaction is allowed to warm to room temperature and stirred for approximately 48 hours. The reaction is then quenched with saturated aqueous NH4Cl, and diluted with saturated aqueous NaHCO3. The reaction mixture is then extracted with dichloromethane. The organic extract is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (diethylamine-methanol-dichloromethane, 1:2:97) to furnish 3-(4-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester as a single diastereomer; MS: (ESI) m/z 315 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (s, 3 H), 1.04 (s, 3 H), 1.59 (br. s., 1 H), 1.65 (s, 3 H), 1.95-2.18 (m, 2 H), 3.90 (s, 3 H), 6.44 (s, 1 H), 6.76 (d, J=7.8 Hz, 1 H), 7.16-7.25 (m, 1 H), 7.37 (t, J=7.6 Hz, 1 H), 7.46 (s, 1 H), 7.66 (d, J=7.8 Hz, 1 H), 7.83 (s, 1 H);
Reaction SMILES: [CH3:1][O:2][C:3](=[O:33])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH:14]([O:16][CH2:17][CH2:18]OC)[CH2:13][CH:12]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(OC([N:41]1CC(OCCOC)C[CH:42]1[C:51]1N(COCC[Si](C)(C)C)C=C(C2C=CC(Br)=CC=2)[N:55]=1)=O)(C)(C)C>>[CH3:1][O:2][C:3](=[O:33])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH:14]([O:16][C:17]2[CH:18]=[N:55][CH:51]=[CH:42][N:41]=2)[CH2:13][CH:12]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]
Reactant: COCCOC1CC(c2nc(-c3ccc(Br)cc3)cn2COCC[Si](C)(C)C)N(C(=O)OC(C)(C)C)C1
Reactant: COCCOC1CC(c2ncc(-c3ccc(Br)cc3)[nH]2)N(C(=O)C(NC(=O)OC)C(C)C)C1
Product: COC(=O)NC(C(=O)N1CC(Oc2cnccn2)CC1c1ncc(-c2ccc(Br)cc2)[nH]1)C(C)C

Procedure:
Title compound was prepared according to the method employed to prepare {1-[2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-(2-methoxy-ethoxy)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (Example 1), substituting 2-[4-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-4-(pyrazin-2-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (94 mg) for 2-[4-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-4-(2-methoxy-ethoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (88 mg, 99%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[C:8]3[NH:16][N:15]=[N:14][C:9]=3[N:10]=[C:11]([NH2:13])[N:12]=2)=[CH:4][CH:3]=1.Br[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][O:26][CH2:27][CH:28]2[CH2:32][CH2:31][CH2:30][O:29]2)[N:20]=1>>[O:29]1[CH2:30][CH2:31][CH2:32][CH:28]1[CH2:27][O:26][CH2:25][C:21]1[N:20]=[C:19]([CH2:18][N:14]2[C:9]3[N:10]=[C:11]([NH2:13])[N:12]=[C:7]([C:5]4[O:6][C:2]([CH3:1])=[CH:3][CH:4]=4)[C:8]=3[N:16]=[N:15]2)[CH:24]=[CH:23][CH:22]=1
Reactant: Cc1ccc(-c2nc(N)nc3nn[nH]c23)o1
Reactant: BrCc1cccc(COCC2CCCO2)n1
Product: Cc1ccc(-c2nc(N)nc3c2nnn3Cc2cccc(COCC3CCCO3)n2)o1

Procedure:
Prepared from 7-(5-methyl-2-furyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ylamine and 2-bromomethyl-6-(tetrahydrofuran-2-ylmethoxymethyl)pyridine by the alkylation method described in Example 36.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20]([C:24]1[CH:50]=[CH:49][C:27]([C:28]([NH:30][C:31]2[CH:47]=[C:46]([NH2:48])[CH:45]=[CH:44][C:32]=2[C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)=[O:34])=[O:29])=[CH:26][CH:25]=1)([CH3:23])([CH3:22])[CH3:21].C1(N=C=NC2CCCCC2)CCCCC1.C1C=NC2N(O)N=NC=2C=1>CN(C)C=O>[C:20]([C:24]1[CH:50]=[CH:49][C:27]([C:28]([NH:30][C:31]2[CH:47]=[C:46]([NH:48][C:17](=[O:19])[C@H:9]([CH2:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:45]=[CH:44][C:32]=2[C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)=[O:34])=[O:29])=[CH:26][CH:25]=1)([CH3:23])([CH3:21])[CH3:22]
Reactant: COc1ccc(NC(=O)c2ccc(N)cc2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Product: COc1ccc(NC(=O)c2ccc(NC(=O)[C@H](Cc3ccccc3)NC(=O)OC(C)(C)C)cc2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.9 %

Procedure:
To a solution of N-(tert-butoxycarbonyl)-L-phenylalanine (130 mg, 0.49 mmol) in N,N-dimethylformamide (5 mL) cooled to 0° C. was added 2-(4-tert-butylbenzoylamino)-4-amino-N-(4-methoxyphenyl)benzamide (240 mg, 0.49 mmol), dicyclohexylcarbodiimide (112 mg, 0.54 mmol), and 7-aza-1-hydroxybenzotriazole (71 mg, 0.52 mmol). After stirring for 1 h, the reaction mixture was allowed to warm to room temperature. After 12 h, the mixture was filtered and the filtrate diluted with ethyl acetate. The solution was washed with 1 N aqueous sodium carbonate solution, 1.5 N aqueous citric acid solution, and water. The organic layer was dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was chromatographed (silica gel, 10% ethyl acetate/90% methylene chloride) to give 195 mg (60%) of the title compound.
Reaction SMILES: [CH2:1]([S:3][C:4](SCC)=[C:5]([C:19]([F:22])([F:21])[F:20])[CH2:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)=[O:8])[CH3:2].[O-:26]Cl.[Na+]>C(O)(C(F)(F)F)=O.O>[CH2:1]([S:3][C:4](=[O:26])[CH:5]([C:19]([F:22])([F:21])[F:20])[CH2:6][C:7](=[O:8])[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)[CH3:2]
Reactant: CCSC(SCC)=C(CC(=O)c1ccc(C(F)(F)F)cc1)C(F)(F)F
Reactant: [O-]Cl
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCSC(=O)C(CC(=O)c1ccc(C(F)(F)F)cc1)C(F)(F)F

Procedure:
A mixture of 4,4-bis-ethylsulfanyl-3-trifluoromethyl-1-(4-trifluoromethyl-phenyl)-but-3-en-1-one (example C.26 step 3) (36.96 g, 92 mmol) in TFA (54.3 mL) and water (5.8 mL) was refluxed for 18 h under nitrogen atmosphere, the exhaust of the reaction was passed through a NaOCl solution to trap the liberated ethyl mercaptane. The volatiles were evaporated and the mixture was diluted with water and extracted with TBME, the organic layer was washed with sat. NaHCO3-sol. and brine, dried over Na2SO4. Removal of the solvent in vacuum left the title compound as a brown oil (31.2 g, 95%), which was used without further purification [according to J. Fluorine Chem. 2001, 107, 281.]. MS (EI) 339.0 [(M−F)+].
Reaction SMILES: Br.[NH2:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([CH2:13][CH2:14][CH3:15])[CH2:8]2.C(=O)(O)[O-].[K+].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[C:26](Cl)=[O:27].C1C2C(=CC=CC=2)CCN1>C1C=CC=CC=1>[CH3:35][O:34][C:30]1[CH:29]=[C:25]([CH:24]=[C:23]([O:22][CH3:21])[C:31]=1[O:32][CH3:33])[C:26]([NH:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([CH2:13][CH2:14][CH3:15])[CH2:8]2)=[O:27]
Reactant: CCCN1CCc2c(N)cccc2C1
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Agent: Br
Agent: O=C([O-])O
Agent: [K+]
Solvent: c1ccccc1
Product: CCCN1CCc2c(cccc2NC(=O)c2cc(OC)c(OC)c(OC)c2)C1

Procedure:
5-Amino-2-n-propyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (13.7 g) prepared as in Example 5 was suspended in dry benzene (100 ml) and 0.5 g of dry potassium bicarbonate was added. A 0.1 mole excess of 3,4,5-trimethoxybenzoyl chloride was dissolved in dry benzene (100 ml) and this solution was added to the solution of the tetrahydroisoquinoline. The mixture was refluxed for 5 days. The precipitate formed was collected by filtration and washed with 10% sodium carbonate solution followed by water. The washings were discarded and the remaining solid (11.7 g) was purified by recrystallization from ethanol to yield 5-(3,4,5-trimethoxybenzamido)-2-n-propyl-1,2,3,4-tetrahydroisoquinoline as a white powder, m.p., 158.5°-159.5° C.
Reaction SMILES: C([N:8]([CH2:16][C@@H:17]1[O:21][C:20](=[O:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:25]([F:35])[CH:24]=2)[CH2:18]1)CC1C=CC=CC=1)C1C=CC=CC=1.CCOCC.N#N.C(O)=O>[Pd].O>[NH2:8][CH2:16][C@@H:17]1[O:21][C:20](=[O:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)=[C:25]([F:35])[CH:24]=2)[CH2:18]1
Reactant: O=C1O[C@@H](CN(Cc2ccccc2)Cc2ccccc2)CN1c1ccc(N2CCOCC2)c(F)c1
Agent: [Pd]
Agent: N#N
Solvent: CCOCC
Solvent: O
Solvent: O=CO
Product: NC[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1
Temperature: 80 °C
Reaction time: 2 h
Yield: 77.9 %

Procedure:
Compound 4 (0.95 g, 2 mmol) and 10% Pd—C (0.02 mmol) were added to 20 mL of ether and the air was replaced with N2. Formic acid (94 mg, 2 mmol) was added and the mixture was stirred at 80° C. for 2 hours, Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated to provide 0.46 g of white solid in 78% yield. HPLC: 99.2%.
Reaction SMILES: Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([CH3:8])[N:7]=1.[CH:10]1([O:16][C:17]2[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=2)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>COCCOC.O.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>[CH:17]1([O:16][C:10]2[CH:15]=[CH:14][C:13]([C:2]3[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([CH3:8])[N:7]=3)=[CH:12][CH:11]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: Cc1cnc(N)c(Br)n1
Reactant: OB(O)c1ccc(OC2CCCCC2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1cnc(N)c(-c2ccc(OC3CCCCC3)cc2)n1
Temperature: 100 °C
Reaction time: 2 h
Yield: 52.2 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (55.3 mg) was added to a suspension of 3-bromo-5-methylpyrazin-2-amine (300 mg), 4-(cyclohexyloxy)phenylboronic acid (456 mg) and sodium carbonate (338 mg) in DME (15 mL) and water (3 mL) and the mixture was stirred at 100° C. under nitrogen for 2 hr. Water and EtOAc were added and the organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane) and washed with hexane/IPE to give the title compound (236 mg) as a white powder.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH2:5][CH:6]2[CH:9]=[O:10]>C(#N)C>[CH3:1][C:2]1([CH3:11])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH2:5][C:6]12[O:10][CH2:9]1
Reactant: CC1(C)C2CCC(C=O)C1C2
Solvent: CC#N
Product: CC1(C)C2CCC3(CO3)C1C2

Procedure:
Material I was used in the procedure described in example 11 in acetonitrile and it was observed that after 2 h of reaction time, the conversion was less than 23% and selectivity for myrtanal was 53%.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][C:9](=[CH2:11])[CH3:10]>>[C:9]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([C:9]([CH3:11])([CH3:10])[CH3:8])[C:1]=1[OH:7])([CH3:10])([CH3:8])[CH3:11]
Reactant: C=C(C)C
Reactant: Oc1ccccc1
Product: CC(C)(C)c1cccc(C(C)(C)C)c1O
Reaction time: 8 h
Yield: 100 %

Procedure:
Phenol and the above-mentioned catalyst are charged into a reactor; the mixture is heated to 100°-110° C. and isobutylene is passed thereinto for 8 hours. The resulting alkylate is subjected to a vacuum-rectification. After recrystallization of the product from aliphatic hydrocarbons, a 100% pure 2,6-di-tertbutylphenol is obtained.
Reaction SMILES: [OH:1][C@H:2]([C:10]1[CH:19]=[CH:18][C:13]2[C:14](=[O:17])[O:15][CH2:16][C:12]=2[C:11]=1[CH3:20])[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[CH3:21][C:22]1[CH:23]=[C:24]([C:31]#[N:32])[CH:25]=[N:26][C:27]=1[CH:28]1[CH2:30][O:29]1>>[OH:29][CH:28]([C:27]1[N:26]=[CH:25][C:24]([C:31]#[N:32])=[CH:23][C:22]=1[CH3:21])[CH2:30][N:7]1[CH2:8][CH2:9][N:4]([CH2:3][C@H:2]([OH:1])[C:10]2[CH:19]=[CH:18][C:13]3[C:14](=[O:17])[O:15][CH2:16][C:12]=3[C:11]=2[CH3:20])[CH2:5][CH2:6]1
Reactant: Cc1cc(C#N)cnc1C1CO1
Reactant: Cc1c([C@@H](O)CN2CCNCC2)ccc2c1COC2=O
Product: Cc1cc(C#N)cnc1C(O)CN1CCN(C[C@H](O)c2ccc3c(c2C)COC3=O)CC1

Procedure:
6-(1-Hydroxy-2-{4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}ethyl)-5-methylpyridine-3-carbonitrile was prepared in a similar fashion to that described for the synthesis of EXAMPLE 58 starting from 5-[(1R)-1-hydroxy-2-(piperazin-1-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one and 5-methyl-6-(oxiran-2-yl)pyridine-3-carbonitrile.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8](Cl)=[O:9])=[CH:4][CH:3]=1.[NH2:11][C:12]1[CH:13]=[C:14]([NH:19][C:20](=[O:30])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N:27]([CH3:29])[CH3:28])[CH:22]=2)[CH:15]=[CH:16][C:17]=1[CH3:18].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O.C(Cl)Cl>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:11][C:12]2[CH:13]=[C:14]([NH:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]([CH3:28])[CH3:29])[CH:22]=3)[CH:15]=[CH:16][C:17]=2[CH3:18])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(NC(=O)c2cccc(N(C)C)c2)cc1N
Reactant: O=C(Cl)c1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1ccc(NC(=O)c2cccc(N(C)C)c2)cc1NC(=O)c1ccc(Cl)nc1
Yield: 14.9 %

Procedure:
6-Chloropyrid-3-ylcarbonyl chloride (0.37 g) was added to a mixture of N-(3-amino-4-methylphenyl)-3-dimethylaminobenzamide (0.54 g), potassium carbonate (0.304 g), DMF (5 ml) and methylene chloride (20 ml) and the resultant mixture was stirred at ambient temperature for 16 hours. The mixture was poured into water and extracted with ethyl acetate. The organic extracts were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 3:2:1 mixture of isohexane, ethyl acetate and methylene chloride as eluent. There was thus obtained the title compound as a solid (0.122 g); NMR Spectrum: (DMSOd6) 2.19 (s, 6H), 3.28 (s, 3H), 6.88 (m, 1H), 7.25 (m, 4H), 7.57 (m, 1H), 7.7 (d, 1H), 7.84 (d, 1H), 8.36 (m, 1H), 8.95 (d, 1H), 10.11 (s, 1H), 10.16 (s, 1H); Mass Spectrum: M+H+ 409 and 411.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:32])[NH:17][C:18]1[S:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29](O)=[O:30])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2[CH:44]=[CH:45][CH:46]=[N:47]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(N)CC1>>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:32])[NH:17][C:18]1[S:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29](=[O:30])[NH:47][CH:46]3[CH2:44][CH2:45]3)=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ccc(-c2cnc(NC(=O)[C@@H]3CCCN3C(=O)OCc3ccccc3)s2)cc1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CC1
Product: O=C(NC1CC1)c1ccc(-c2cnc(NC(=O)[C@@H]3CCCN3C(=O)OCc3ccccc3)s2)cc1

Procedure:
From (S)-2-[5-(4-carboxy-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester (Compound 5353, Example 353, 0.04 g, 0.09 mmol), HATU (0.044 g, 0.12 mmol), and (0.03 mL, 0.36 mmol) of cyclopropylamine using General Procedure 3F. 1HNMR (DMSO-d6) δ(ppm)12.44-12.42 (d, 1H), 8.43 (s, 1H), 7.99-7.65 (m, 5H), 7.35-7.10 (m, 4 H), 5.06-4.89 (m, 2H), 4.5-4.46 (m, 1H), 2.83 (s, 2H), 2.25 (m, 1H), 1.91 (m, 3H), 0.70-0.57, (m, 4H); MS: 491.1 (M+H+).
Reaction SMILES: Cl[C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH2:19]1[O:28][C:27]2[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][C:21]=2[O:20]1.O1CCN(C2C3N=C(C4C=CC(F)=CC=4)C=CC=3N=CN=2)CC1>>[CH2:19]1[O:28][C:27]2[CH:26]=[CH:25][C:23]([NH:24][C:2]3[C:3]4[N:11]=[C:10]([C:12]5[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=5)[CH:9]=[CH:8][C:4]=4[N:5]=[CH:6][N:7]=3)=[CH:22][C:21]=2[O:20]1
Reactant: Nc1ccc2c(c1)OCO2
Reactant: Fc1ccc(-c2ccc3ncnc(Cl)c3n2)cc1
Agent: Fc1ccc(-c2ccc3ncnc(N4CCOCC4)c3n2)cc1
Product: Fc1ccc(-c2ccc3ncnc(Nc4ccc5c(c4)OCO5)c3n2)cc1
Yield: 94 %

Procedure:
was synthesized from 4-chloro-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine and 3,4-(methylendioxy)aniline in 94% yield, using the procedure described for the synthesis of 4-morpholino-6-(4-fluorophenyl)-pyrido[3,2-d]pyrimidine. The mass spectrum characterising data was as follows: MS (m/z): 361 ([M+H]+, 100).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:24]([O:26]CC)=[CH2:25])[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C1COCC1>[C:24]([C:11]1[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:10]=1)(=[O:26])[CH3:25]
Reactant: C=C(OCC)c1cc(OCc2ccccc2)cc2nc(NC(=O)NCC)sc12
Agent: Cl
Solvent: C1CCOC1
Product: CCNC(=O)Nc1nc2cc(OCc3ccccc3)cc(C(C)=O)c2s1
Temperature: 25 °C
Reaction time: 4 h
Yield: 70 %

Procedure:
1-[5-benzyloxy-7-(1-ethoxyvinyl)-1,3-benzothiazol-2-yl]-3-ethyl-urea was dissolved in THF (24 mL) and 2M aqueous hydrochloric acid (2 mL) was added and the reaction stirred at ambient temperature for 4 h, after which time LCMS indicated clean conversion to the ketone. The reaction solvent was removed in vacuo to give the desired compound (650 mg, 70% yield).
Reaction SMILES: [OH:1][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][C:17]([OH:19])=[O:18].N1C=CC=CC=1.[C:26](Cl)(=[O:42])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>O1CCCC1>[C:26]([O:1][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][C:17]([OH:19])=[O:18])(=[O:42])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: O=C(O)CCCCCCCCCCCCCCCO
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.7 %

Procedure:
16-Hydroxyhexadecanoic acid (5.43 g, 19.9 mmol) was dissolved in tetrahydrofuran (190 ml) and pyridine (2.36 g, 29.9 mmol) was added. Palmitoyl chloride (5.48 g, 19.9 mmol) was dissolved in tetrahydrofuran (10 ml) and added dropwise at room temperature. After stirring at room temperature for 16 hours, the mixture was filtered and the filtrate evaporated under reduced pressure. The residue was dissolved in chloroform, washed with water (3×50 ml), and the organc phase was dried (MgSO4). After evaporating under reduced pressure, the residue was purified on a silica column, eluted with chloroform with increasing methanol concentration (from 1% to 2% methanol in chloroform) to give 8.41 g (83%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 0.85 (t, 3H, CH3), 1.20-1.35 (s, 46H, --CH2 --), 1.55-1.70 (m, 6H, --CH2 --), 2.25 (t, 2H, --CH2 --C(O)--O), 2.45 (t, 2H, --CH2 --COOH), 4.05 (t, 2H, --O--CH2). 13C NMR (75 MHz, CDCl3): δ 14.01, 22.57, 24.10, 24.91, 25.82, 28.53, 28.75, 28.94, 29.08, 29.15, 29.25, 29.36, 29.54, 31.81, 34.29, 35.16, 64.27, 76.48, 76.90, 77.10, 77.32, 169.50, 173.91.