Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O-])=O>O>[CH:6]1[C:7]2[C:2](=[N:1][C:12]3[C:11]([N:8]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:3]=[CH:4][CH:5]=1
Reactant: Nc1ccccc1
Reactant: O=[N+]([O-])c1ccccc1
Solvent: O
Product: c1ccc2nc3ccccc3nc2c1
Reaction time: 0.17 h

Procedure:
86.24 gms of 25% aqueous TMA(OH) was added to 102.8 ml of deionized water. 107.8 gm of calcined and protonated ZSM-5 was added to form a slurry that was mixed vigorously at 40° C. for 3 hours and 15 minutes. The ion-exchanged material was filtered. The filtrate was kept aside for use in subsequent loadings. To make a 20% loading of TMA(OH) in the zeolite, 154.8 gms of 25% by weight of aqueous TMA(OH) was added to the cake. The resulting slurry was transferred to a rotary evaporator. The temperature of the heating medium was controlled at 40° C. and the rotary evaporator was equipped with a vacuum pump. The drying time was adjusted depending on the vacuum pressure at given temperature. It is preferred to run the drying temperature of not nore than 80° C. The most suitable temperature is 40° C. to reduce the level of TMA(OH) decomposition. For this example, the pressure was controlled at 13 mm Hg at 40° C. Drying was allowed to proceed for about an hour and 10 minutes. The resulting material produced a thick paste that was flowable. This material was transferred to a flat evaporating dish and allowed to further dry at about 35° C. for 15 hours in a vacuum desiccator. The dried solid was not hard and very easy to grind. The coupling reaction test, which consists of reacting aniline and nitrobenzene did not produce phenazine using the above prepared material.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[N:8]1[CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:19][C:7]1=[C:6]([C:26]([OH:28])=[O:27])[C:5]2=[O:29].C(=O)(O)[O-].[K+].Br[CH2:36][C:37]1[O:38][C:39](=[O:43])[O:40][C:41]=1[CH3:42]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([CH2:36][C:37]3[O:38][C:39](=[O:43])[O:40][C:41]=3[CH3:42])[CH2:14][CH2:13]1)[N:8]1[CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:19][C:7]1=[C:6]([C:26]([OH:28])=[O:27])[C:5]2=[O:29]
Reactant: Cc1oc(=O)oc1CBr
Reactant: O=C(O)c1c2n(c3cc(N4CCNCC4)c(F)cc3c1=O)C(c1ccccc1)S2
Agent: O=C([O-])O
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1oc(=O)oc1CN1CCN(c2cc3c(cc2F)c(=O)c(C(=O)O)c2n3C(c3ccccc3)S2)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 34.1 %

Procedure:
6-Fluoro-4-oxo-1-phenyl-7-(1-piperazinyl)-4H-[1,3]-thiazeto-[3,2-a]quinoline-3-carboxylic acid (3.0 g) and 0.88 g of potassium bicarbonate were suspended in 50 ml of N,N-dimethylformamide, 1.69 g of 4-bromomethyl-5-methyl-1,3-dioxolen-2-one was dropped thereinto with ice cooling, and the mixture was stirred for 3 hours. After the reaction, the mixture was poured into ice water, the crystals separated out therefrom was collected by filtration, washed with water, dried in vacuo, and the resulting crude crystals were recrystallized from chloroform-ethanol to give 1.3 g of desired product, m.p.201°-202° C. (decompn.).
Reaction SMILES: C([O:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:32][CH2:33][O:34][CH3:35])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][C:18]=2/[CH:36]=[CH:37]\[CH3:38])[CH2:13][CH2:12]1)C1C=CC=CC=1>CO.[C].[Pd]>[F:26][C:24]([F:25])([F:27])[C:23]([C:20]1[CH:21]=[CH:22][C:17]([N:14]2[CH2:13][CH2:12][N:11]([CH2:10][CH2:9][OH:8])[CH2:16][CH2:15]2)=[C:18]([CH2:36][CH2:37][CH3:38])[CH:19]=1)([O:32][CH2:33][O:34][CH3:35])[C:28]([F:31])([F:30])[F:29]
Reactant: C/C=C\c1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1N1CCN(CCOCc2ccccc2)CC1
Agent: [Pd]
Solvent: CO
Product: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1N1CCN(CCO)CC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 28.2 %

Procedure:
(Z)-1-[2-(benzyloxy)ethyl]-4-{4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl]-2-(prop-1-en-1-yl)phenyl}piperazine (33 mg, 0.0604 mmol) was dissolved in methanol (4 mL), added palladium carbon (3.3 mg), and the mixture was stirred at room temperature for 12 hours under a hydrogen atmosphere. The reaction solution was filtered through a pad of celite, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/acetone). The title compound (7.8 mg (yield 24%)) was obtained as a yellow oil.
Reaction SMILES: [C:1]([N:3]=[C:4]1[NH:8][CH2:7][CH2:6][S:5]1)#[N:2].[Cl:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14]Cl)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:1]([N:3]=[C:4]1[N:8]([CH2:14][C:13]2[CH:16]=[CH:17][C:10]([Cl:9])=[CH:11][CH:12]=2)[CH2:7][CH2:6][S:5]1)#[N:2]
Reactant: ClCc1ccc(Cl)cc1
Reactant: N#CN=C1NCCS1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: N#CN=C1SCCN1Cc1ccc(Cl)cc1
Yield: 82.9 %

Procedure:
3,82 g (30 moles) of 2-cyanimino-thiazolidine, 4.9 g (30 mmoles) of 4-chlorobenzyl chloride and 4.3 g of anhydrous potassium carbonate are boiled in 100 ml of acetone for 5 hours. The inorganic salt is filtered off and the acetonic solution is evaporated. The residue is crystallized from 40 ml of isopropanol to yield 6.26 g (83%) of 2-cyanimino-3(4-chlorobenzyl)-thiazolidine, melting at 131° to 133° C. The product is isolated by filtration.
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]([C:7]2[C:12]([F:13])=[CH:11][C:10]([C:14]([OH:17])([CH3:16])[CH3:15])=[CH:9][C:8]=2[F:18])=[N:4][C:3]=1[C:19]([NH2:21])=[O:20].Br[C:23]1[N:28]=[C:27]([CH2:29][O:30][CH2:31][C:32]([CH3:35])([OH:34])[CH3:33])[CH:26]=[CH:25][CH:24]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:13][C:12]1[CH:11]=[C:10]([C:14]([OH:17])([CH3:16])[CH3:15])[CH:9]=[C:8]([F:18])[C:7]=1[C:5]1[S:6][C:2]([NH:1][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]([CH2:29][O:30][CH2:31][C:32]([OH:34])([CH3:33])[CH3:35])[N:28]=2)=[C:3]([C:19]([NH2:21])=[O:20])[N:4]=1
Reactant: CC(C)(O)COCc1cccc(Br)n1
Reactant: CC(C)(O)c1cc(F)c(-c2nc(C(N)=O)c(N)s2)c(F)c1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: CC(C)(O)COCc1cccc(Nc2sc(-c3c(F)cc(C(C)(C)O)cc3F)nc2C(N)=O)n1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
A sealed tube was charged with a stir bar, 5-amino-2-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-1,3-thiazole-4-carboxamide (Example 15, Step 5) (150 mg, 0.48 mmol), 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (125 mg, 0.48 mmol), Pd2(dba)3 (44 mg, 0.048 mmol), X-PHOS (114 mg, 0.24 mmol), and potassium carbonate (66 mg, 0.48 mmol) were added. The tube was evacuated and backfilled with argon 3×. Fully degassed tert-amyl alcohol (0.95 ml) was added and the reaction vessel was sealed and left to stir at 100° C. overnight. The reaction vessel was removed from the heat and allowed to cool to room temperature. The reaction mixture was taken up in ethyl acetate and washed with 100 mL water. The water layer was treated with concentrated ammonium hydroxide and extracted with ethyl acetate. The organic fractions were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The compound on silica was purified by reverse phase chromatography (10-100% acetonitrile/water+0.05% TFA modifier). Desired fractions were poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduce pressure to afford the title compound as a yellow solid. 1H NMR (500 MHz, d6-DMSO) δ 11.37 (s, 1H), 7.76 (t, 1H), 7.66 (s, 1H), 7.53 (s, 1H), 7.32 (d, 2H), 7.16 (d, 1H), 7.05 (d, 1H), 4.59 (s, 2H), 3.29 (s, 2H), 1.44 (s, 6H), 1.09 (s, 6H). Hydroxyl protons were not observed. LRMS (APCI) calc'd for C23H27F2N4O4S [M+H]+: 493.2, found 493.2.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:13][CH:14]2[CH2:16][CH2:15]2)=[C:4]([CH:8]=[C:9]([F:12])[C:10]=1[F:11])[C:5]([OH:7])=O.[C:17]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])(=[O:20])[NH:18][NH2:19].C(N=C=NCCCN(C)C)C>ClCCl>[C:22]([O:21][C:17]([N:18]([C:5](=[O:7])[C:4]1[CH:8]=[C:9]([F:12])[C:10]([F:11])=[C:2]([Cl:1])[C:3]=1[NH:13][CH:14]1[CH2:16][CH2:15]1)[NH2:19])=[O:20])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)OC(=O)NN
Reactant: O=C(O)c1cc(F)c(F)c(Cl)c1NC1CC1
Agent: CCN=C=NCCCN(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N(N)C(=O)c1cc(F)c(F)c(Cl)c1NC1CC1
Reaction time: 16 h
Yield: 63.1 %

Procedure:
To a solution of 3-chloro-2-cyclopropylamino-4,5-difluorobenzoic acid (Example 5d, 2.09 g, 8.45 mmol) in dichloromethane (30 mL) is added tert-butyl carbazate (1.67 g, 12.7 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (2.43 g, 12.7 mmol). After 16 hours, the reaction mixture is diluted with dichloromethane and washed with saturated NaHCO3, water, and brine. The organic layer is dried over MgSO4 and filtered. The filtrate is concentrated under vacuum and purified via flash column chromatography (1:2 ethyl acetate/hexanes) to afford the title compound (1.93 g). MS EI: m/z 360 (M+).
Reaction SMILES: [C:1]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].C(N(CC)CC)C.[CH:25]([C:28]1[CH:37]=[CH:36][CH:35]=[C:34]([CH:38]([CH3:40])[CH3:39])[C:29]=1[O:30][C:31](Cl)=[O:32])([CH3:27])[CH3:26]>ClCCl.CN(C1C=CN=CC=1)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH:25]([C:28]1[CH:37]=[CH:36][CH:35]=[C:34]([CH:38]([CH3:40])[CH3:39])[C:29]=1[O:30][C:31]([O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])=[O:32])([CH3:27])[CH3:26]
Reactant: O=C(OCc1ccccc1)c1ccccc1O
Reactant: CC(C)c1cccc(C(C)C)c1OC(=O)Cl
Agent: CN(C)c1ccncc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)c1cccc(C(C)C)c1OC(=O)Oc1ccccc1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 57 %

Procedure:
To a cooled (0° C.) solution of benzyl salicylate (0.77 g, 3.3 mmol) in dichloromethane (6 mL) was added triethylamine (0.52 mL, 3.7 mmol) and a catalytic amount of DMAP. To this mixture a suspension of compound (104) (0.9 g, 3.7 mmol, crude product from last step) in dichloromethane (4 mL) was further added. The reaction was allowed to warm to room temperature slowly and stirred for 14 h. The reaction mixture was then diluted with 10% aqueous citric acid solution (10 mL) and extracted with ethyl ether (2×40 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was purified by radial chromatography on silica gel (eluting with ethyl acetate/hexane) to afford 0.8 g (57% yield over two steps) of the title compound (105).
Reaction SMILES: CO.[CH2:3]([O:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[CH:21]=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([O-])(=O)C.[Na+].Cl.[NH2:29][OH:30]>O>[CH2:3]([O:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]=1[CH:21]=[N:29][OH:30])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: NO
Reactant: O=Cc1c(OCc2ccccc2)ccc2ccccc12
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Product: ON=Cc1c(OCc2ccccc2)ccc2ccccc12
Yield: 97.8 %

Procedure:
To 460 ml of methanol and 150 ml of water were added 120 g (0.46 mole) of 2-benzyloxy-1-naphthaldehyde, 75 g (0.92 mole) of sodium acetate and 48 g (0.69 mole) of hydroxylamine hydrochloride, and the mixture was refluxed by heating for 2 hours. After the reaction, the reaction mixture was added to 1.5 liters of water. The precipitated crystals were collected by filtration to obtain 125 g (0.45 mole) of 2-benzyloxy-1-naphthaldoxime.
Reaction SMILES: C1(C(C2C=CC=CC=2)([C@@H]2CCCN2)O)C=CC=CC=1.B.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[C:29]([C:43](=O)[C:44]3[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH2:52][N:53]4[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]4)=[CH:46][CH:45]=3)=[C:30]3[C:35](=[CH:36][CH:37]=2)[CH:34]=[C:33]([O:38][S:39]([CH3:42])(=[O:41])=[O:40])[CH:32]=[CH:31]3)=[C:24]([S:60]C)[CH:23]=1.C(CN)O.[Cl-].[NH4+].C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>C1COCC1>[F:21][C:22]1[CH:23]=[C:24]2[C:25](=[CH:26][CH:27]=1)[C:28]1[C:29](=[C:30]3[C:35](=[CH:36][CH:37]=1)[CH:34]=[C:33]([O:38][S:39]([CH3:42])(=[O:40])=[O:41])[CH:32]=[CH:31]3)[CH:43]([C:44]1[CH:45]=[CH:46][C:47]([O:50][CH2:51][CH2:52][N:53]3[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]3)=[CH:48][CH:49]=1)[S:60]2
Reactant: CSc1cc(F)ccc1-c1ccc2cc(OS(C)(=O)=O)ccc2c1C(=O)c1ccc(OCCN2CCCCC2)cc1
Agent: B
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: NCCO
Product: CS(=O)(=O)Oc1ccc2c3c(ccc2c1)-c1ccc(F)cc1SC3c1ccc(OCCN2CCCCC2)cc1
Temperature: 45 °C
Reaction time: 3 h
Yield: 88.1 %

Procedure:
Charge a flask with (s)-(−)-α,α-diphenyl-2-pyrrolidinemethanol (380 mg, 1.5 mmol), dissolve with 1M borane in THF (60 mL, 60 mmol), purge with nitrogen and heat to 45° C. Dissolve methanesulfonic acid 6-(4-fluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (9.0 g, 15.1 mmol) in dry THF (80 mL) and add to the borane solution via syringe pump over 2 hours. After the addition is complete, add ethanolamine (18.2 mL, 300 mmol) and stir at 45° C. for 3 hours. Pour the reaction into saturated aqueous ammonium chloride and extract with methylene chloride. Dry over sodium sulfate, filter and concentrate to a beige foam. Dissolve the crude foam in dry THF (150 mL). Add triethylamine (12.4 mL, 90 mmol) and methanesulfonyl chloride (7.0 mL, 90 mmol) and heat to reflux under nitrogen. Add more methanesulfonyl chloride (0.45 mL, 5.8 mmol) after 2 hours to drive the reaction to completion. Pour the reaction into saturated aqueous sodium bicarbonate and extract twice with methylene chloride. Dry the combined organic layers with sodium sulfate, filter and concentrate. Purify the residue on silica gel (0% to 4% methanol in methylene chloride) to yield 7.5 g (88%) of the title compound. HPLC Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=2.96 min (100%); mass spectrum (ion spray): m/z=564.3 (M+H).
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:12](O)=[O:13])[CH:9]=2)[NH:4][CH:3]1[C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:17][CH:16]=1.[CH:28]1([S:31]([NH2:34])(=[O:33])=[O:32])[CH2:30][CH2:29]1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][C:2]1([CH3:27])[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:12]([NH:34][S:31]([CH:28]3[CH2:30][CH2:29]3)(=[O:33])=[O:32])=[O:13])[CH:9]=2)[NH:4][CH:3]1[C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:19][CH:20]=1
Reactant: NS(=O)(=O)C1CC1
Reactant: CC1(C)Cc2cc(C(=O)O)ccc2NC1c1ccc(N2CCOCC2)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC1(C)Cc2cc(C(=O)NS(=O)(=O)C3CC3)ccc2NC1c1ccc(N2CCOCC2)cc1
Temperature: 65 °C
Yield: 26.9 %

Procedure:
A mixture of 3,3-dimethyl-2-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (70 mg, 0.19 mmol), 1-3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (55 mg, 0.29 mmol), 4-dimethylaminopyridine (35 mg, 0.29 mmol), cyclopropane sulfonamide (69 mg, 0.57 mmol) in dichloromethane (10 mL) was heated for at 65° C. for 12 hours. Removal of the solvent afforded an oil residue. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water) afforded cyclopropanesulfonic acid [3,3-dimethyl-2-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (24 mg, 27%) as a light yellow solid: LC/MS m/e calcd for C25H31N3O4S (M+H)+: 470.6, observed: 470.3.
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][CH:9]([OH:11])[C:5](=[C:6]([CH3:8])[CH3:7])[CH2:4][CH2:3]1>[Pd].[C].C(OCC)(=O)C>[CH3:1][C@H:2]1[CH2:10][C@@H:9]([OH:11])[C@@H:5]([CH:6]([CH3:8])[CH3:7])[CH2:4][CH2:3]1
Reactant: CC(C)=C1CCC(C)CC1O
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)[C@H]1CC[C@@H](C)C[C@H]1O
Temperature: 60 °C
Reaction time: 5 h
Yield: 90 %

Procedure:
A 100 ml capacity autoclave was charged with 1.0 g (6.5 mmol) of pulegol, 5% Pd-carbon (20 mg) and ethyl acetate (5 ml), and the mixture was stirred at 60° C. for 5 hours under a hydrogen pressure of 2 Mpa. After completion of the reaction, the reaction solution was cooled to room temperature and concentrated. A 0.99 g portion of a mixture of menthol:neoisomenthol=91:9 was obtained. The yield was 90%.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][NH2:11])[CH2:4][CH2:3]1.[CH2:12]([O:14][C:15]([C:17]1[C:18](=[O:37])[C:19]2[CH:24]=[N:23][C:22](S(C)(=O)=O)=[N:21][C:20]=2[N:29]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:30]=1)=[O:16])[CH3:13]>>[CH2:12]([O:14][C:15]([C:17]1[C:18](=[O:37])[C:19]2[CH:24]=[N:23][C:22]([NH:11][CH2:10][CH2:9][CH2:8][N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[N:21][C:20]=2[N:29]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)[CH:30]=1)=[O:16])[CH3:13]
Reactant: CN1CCN(CCCN)CC1
Reactant: CCOC(=O)c1cn(C2CCCCC2)c2nc(S(C)(=O)=O)ncc2c1=O
Product: CCOC(=O)c1cn(C2CCCCC2)c2nc(NCCCN3CCN(C)CC3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 28 Step F, the title compound was prepared from 3-(4-methyl-piperazin-1-yl)-propylamine and 8-cyclohexyl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (20 mg, 0.04 mmol). 8-Cyclohexyl-2-[3-(4-methyl-piperazin-1-yl)-propylamino]-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester was obtained as a white solid (17 mg, 80%). Mass Spectrum (LCMS, ESI pos.) Calcd. For C24H36N6O3: 457.28 (M+H). Found: 457.3.
Reaction SMILES: [N+:1]([C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[CH2:6][NH:7][CH2:8][CH2:9][CH2:10][OH:11])([O-:3])=[O:2].C(N(CC)CC)C.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.O>C(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[CH2:6][N:7]1[CH2:8][CH2:9][CH2:10][O:11][C:24]1=[O:26])([O-:3])=[O:2]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: O=[N+]([O-])c1ccccc1CNCCCO
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: O
Product: O=C1OCCCN1Cc1ccccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 63 %

Procedure:
3-(2-Nitrobenzylamino)-1-propanol (1.03 g, 4.90 mmol) was dissolved in chloroform (20 ml) and the reaction solution was cooled to 0° C. Then triethylamine (1.98 g, 19.6 mmol), triphosgene (0.58 g, 1.95 mmol) were added thereto and the mixture was stirred at the same temperature for 1.5 hours. The reaction mixture was added with water and extracted with ethyl acetate and after the organic layer was washed with a saturated brine, it was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:4) and 3-(2-nitrobenzyl)-[1,3]-oxazinan-2-one (0.29 g) was obtained.
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH2:12]O)=[C:10]([CH3:14])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:15]([O:19][C:20](=[O:33])[CH2:21][C:22]([OH:32])([C:25]1[CH:30]=[CH:29][NH:28][C:27](=[O:31])[CH:26]=1)[CH2:23][CH3:24])([CH3:18])([CH3:17])[CH3:16].C(P(CCCC)CCCC)CCC.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:15]([O:19][C:20](=[O:33])[CH2:21][C:22]([C:25]1[CH:30]=[CH:29][N:28]([CH2:12][C:11]2[C:2]([Cl:1])=[N:3][C:4]3[C:9]([C:10]=2[CH3:14])=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:27](=[O:31])[CH:26]=1)([OH:32])[CH2:23][CH3:24])([CH3:16])([CH3:17])[CH3:18]
Reactant: Cc1c(CO)c(Cl)nc2ccccc12
Reactant: CCC(O)(CC(=O)OC(C)(C)C)c1cc[nH]c(=O)c1
Agent: CCCCP(CCCC)CCCC
Agent: CCOC(=O)N=NC(=O)OCC
Solvent: C1CCOC1
Product: CCC(O)(CC(=O)OC(C)(C)C)c1ccn(Cc2c(Cl)nc3ccccc3c2C)c(=O)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 39.4 %

Procedure:
A mixture, under an argon atmosphere, of 2-chloro-4-methyl-3-quinolinemethanol (obtained according to 3.c, 2.08 g, 10 mmol), of tert-butyl3-hydroxy-3-(2-oxo-1,2-dihydro-4-pyridinyl)pentanoate (obtained according to 1.h, 2 g, 11 mmol), and tributylphosphine (2.75 ml, 11 mmol) in anhydrous tetrahydrofuran (40 ml) is treated dropwise with diethyl azodicarboxylate (2.6 ml, 15 mmol). The reaction mixture is then agitated at ambient temperature for 6 hours, then concentrated under reduced pressure. The resulting oily residue is taken up in dichloromethane (200 ml) and washed with saturated aqueous ammonium chloride then with saturated aqueous sodium chloride. The organic phase is dried over sodium sulphate then concentrated to 5 ml and acetonitrile is added in order to obtain a white precipitate which is kept at 4° C. for 16 hours. The precipitate is collected by filtration then washed with isopropyl ether in order to produce 1.8 g (39%) of a white solid.
Reaction SMILES: [ClH:1].[CH:2]1([C:8]2[CH:16]=[CH:15][C:11]([CH:12]([NH2:14])[CH3:13])=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.Cl.C[CH:19]([NH2:34])[C:20]1C=[CH:24][C:23](CCC2C=CC=CC=2)=[CH:22][CH:21]=1>>[ClH:1].[CH:2]1([C:8]2[CH:9]=[CH:10][C:11]([CH:12]([N:14]=[C:19]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][NH:34]3)[CH3:13])=[CH:15][CH:16]=2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: CC(N)c1ccc(CCc2ccccc2)cc1
Reactant: CC(N)c1ccc(C2CCCCC2)cc1
Agent: Cl
Product: CC(N=C1CCCCCN1)c1ccc(C2CCCCC2)cc1

Procedure:
Following essentially the same procedure described in Example 7 above and substituting p-cyclohexyl-α-methylbenzylamine hydrochloride for the α-methyl-p-phenyethylbenzylamine hydrochloride above, results in the formation of 2-(p-cyclohexyl-α-methylbenzylimino)-hexahydroazepine hydrochloride having a M.P. of 245°-7° C.
Reaction SMILES: [C:1]1([C:7]2[O:11][CH:10]=[N:9][C:8]=2[C:12]([OH:14])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:27][CH2:28][CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>O1CCCC1>[C:1]1([C:7]2[O:11][CH:10]=[N:9][C:8]=2[C:12]([NH:27][CH2:28][CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:14])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: O=C(O)c1ncoc1-c1ccccc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCNC(=O)c1ncoc1-c1ccccc1
Reaction time: 0.5 h
Yield: 92.1 %

Procedure:
3.6 g (19.1 mmol) of 5-phenyl-4-oxazolecarboxylic acid were added portionwise to a suspension of 3.1 g (19.1 mmol) of 1,1'-carbonyldiimidazole in 20 ml of dry tetrahydro-furan, whereby a brown solution formed with o the evolution of gas. After a reaction period of 15 minutes at 20° 3.05 g (19.0 mmol) of t-butyl (2-aminoethyl)carbamate in 10 ml of dry tetrahydrofuran were added dropwise (slight warming) and the reaction mixture was stirred for a further 30 minutes. Thereafter, the reaction mixture was evaporated under reduced pressure and the residue was partitioned between methylene chloride and 0.1 N hydrochloric acid. After washing neutral with saturated sodium chloride solution the organic phase was dried over magnesium sulfate and evaporated, whereby there were obtained 5.8 g (92%) of t-butyl [2-(5-phenyl-4-oxazole- carboxamido)ethyl]- carbamate which were stirred at 20° for 20 minutes in 20 ml of trifluoroacetic acid. Thereafter, the reaction mixture was evaporated under reduced pressure. The residue was dissolved in 5 ml of methanol and treated with 10 ml of 5.5 N hydrogen chloride in methanol. Filtration of the separated crystals yielded 2.4 g (51%) of N-(2-aminoethyl)-5-phenyl-4-oxazole- carboxamide hydrochloride as white crystals, melting point 257° (dec.). The 5-phenyl-4-oxazolecarboxylic acid used as the starting material was prepared as follows: Analogously to the method described in Tetrahedron Letters, 23, 235-236 (1982), from ethyl isocyanoacetate, benzoic acid, phosphoric acid diphenyl ester azide and potassium carbonate in dimethylformamide/water there was prepared ethyl 5-phenyl-4-oxazolecarboxylate which was then converted into the desired acid likewise according to known methods by hydrolysis with 2N sodium hydroxide solution at 50° during 15 minutes.