Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[C:3]=1[C:4](Cl)=[O:5].[C:13]1([P:19]([O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:20]CC)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(Cl)C>C(N(CC)CC)C>[C:13]1([P:19]([C:4](=[O:5])[C:3]2[C:2]([CH3:1])=[CH:10][C:9]([CH3:11])=[CH:8][C:7]=2[CH3:12])(=[O:20])[O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CCOP(Oc1ccccc1)c1ccccc1
Reactant: Cc1cc(C)c(C(=O)Cl)c(C)c1
Agent: CCCl
Solvent: CCN(CC)CC
Product: Cc1cc(C)c(C(=O)P(=O)(Oc2ccccc2)c2ccccc2)c(C)c1
Temperature: 115 °C
Reaction time: 2 h
Yield: 81 %

Procedure:
96.4 g (0.528 mol) of 2,4,6-trimethylbenzoyl chloride and 1.2 g of triethylamine were heated to 115° C. and 65 g (0.264 mol) of monoethyl monophenyl phenylphosphonite were added dropwise in 75 minutes under a nitrogen atmosphere and with vigorous stirring. Ethyl chloride was given off as gas and was condensed in a downstream cold trap. The mixture was then further stirred for 2 hours at 115° C. and simultaneously a relatively strong nitrogen stream was passed through the apparatus. In total, at the end of the reaction 16 g (94% of theory) of ethyl chloride were situated in the cold trap. The excess 2,4,6-trimethylbenzoylchloride was then distilled off at 1 mbar and the residue was distilled with the aid of a thin-film evaporator (bath temperature: 230° C.; 0.3 mbar). 78 g were obtained. The yield was 81% of theory.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([CH:19](OC)OC)[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[C:24]([C@@H:28]([C@H:30]([C:32]([O:34][CH3:35])=[O:33])[OH:31])[OH:29])([O:26][CH3:27])=[O:25]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([CH:19]3[O:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH:28]([C:24]([O:26][CH3:27])=[O:25])[O:29]3)[CH:13]=2)=[N:4][CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1
Reactant: COC(OC)c1cc(-c2ncc(C(F)(F)F)cc2Cl)ccc1Cl
Reactant: COC(=O)[C@H](O)[C@@H](O)C(=O)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COC(=O)C1OC(c2cc(-c3ncc(C(F)(F)F)cc3Cl)ccc2Cl)OC1C(=O)OC
Yield: 76.2 %

Procedure:
3.0 g of 3-chloro-2-(4-chloro-3-dimethoxymethylphenyl)-5-trifluoromethyl-pyridine, 5.4 g of dimethyl L(+)-tartrate and 100 mg of p-toluenesulfonic acid in 180 ml of anhydrous toluene were refluxed for 10 hours. The solution was cooled and then washed with 50 ml of 10% by weight sodium bicarbonate solution and three times with 50 ml of water each time, dried over sodium sulfate and concentrated. Chromatography on silica gel resulted in 3.0 g (77%) of colorless crystals; melting point: 48°-53° C.
Reaction SMILES: [CH:1]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=[C:3](N)[CH:2]=1.N([O-])=O.[Na+].O(CC)[C:16]([S-])=[S:17].[K+].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[K+].S(OC)(OC)(=O)=O.[ClH:37]>>[ClH:37].[CH3:16][S:17][C:2]1[CH:1]=[C:6]([CH:5]=[CH:4][CH:3]=1)[C:7]([OH:9])=[O:8]
Reactant: CCOC(=S)[S-]
Reactant: Nc1ccc(C(=O)O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: O=N[O-]
Solvent: COS(=O)(=O)OC
Product: CSc1cccc(C(=O)O)c1

Procedure:
The aminobenzoic acid (54.8 g, 0.4 mol) was diazotized in the usual manner with sodium nitrite (27.6 g, 0.4 mol) and hydrochloric acid (40 mL) and the resulting diazonium salt solution poured into a hot (70° C.), freshly prepared solution of potassium ethyl xanthate (64.2 g, 0.4 mol) containing sodium carbonate (55.2 g, 0.4 mol) to neutralize acid in the diazonium salt solution. After the reaction was over, as indicated by the cessation of the evolution of gases, the mixture was cooled. It was then treated with potassium hydroxide (24.7 g, 0.44 mol) and dimethyl sulfate (50.4 g, 0.4 mol). The mixture was refluxed for 5 hours. On acidification with hydrochloric acid, the desired product was obtained (38.2 g, 57%). MS: 167.8 (M+1+).
Reaction SMILES: C[N:2]([C:8]1[C:13](=[O:14])[C:12]2[CH:15]=[C:16]([CH2:19][CH2:20][CH2:21][CH3:22])[CH:17]=[CH:18][C:11]=2[S:10][CH:9]=1)[C:3]([C:5](N)=[O:6])=[O:4].[OH-:23].[Na+]>C(O)C.O>[CH2:19]([C:16]1[CH:17]=[CH:18][C:11]2[S:10][CH:9]=[C:8]([NH:2][C:3](=[O:4])[C:5]([OH:6])=[O:23])[C:13](=[O:14])[C:12]=2[CH:15]=1)[CH2:20][CH2:21][CH3:22]
Reactant: [OH-]
Reactant: CCCCc1ccc2scc(N(C)C(=O)C(N)=O)c(=O)c2c1
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCCCc1ccc2scc(NC(=O)C(=O)O)c(=O)c2c1

Procedure:
6.15 g (0.0193 mol) of N-[6-(n-butyl)-4H-1-benzothiopyran-4-on-3-yl]-oxamide methyl ester are stirred with a solution of 22.6 ml of 1N sodium hydroxide solution in 147 ml of ethanol and 970 ml of water for 2 hours at 70°. A small degree of cloudiness is then removed by filtration and the filtrate is acidified with hydrochloric acid, a crystalline product being precipitated. After cooling, the crystals are filtered with suction and washed first with water, then with ethanol and subsequently with ether. After drying there is obtained N-[6-(n-butyl)-4H-1-benzothiopyran-4-on-3-yl)-oxalic acid monoamide having a melting point of 208° (decomposition).
Reaction SMILES: CO[C:3](=[O:21])[C@H:4]([CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[NH2:5].N[C@H](C(O)=O)CCCCN.[CH3:32][N:33]=[C:34]=[S:35]>C(#N)C>[CH2:14]([O:13][C:11]([NH:10][CH2:9][CH2:8][CH2:7][CH2:6][CH:4]1[NH:5][C:34](=[S:35])[N:33]([CH3:32])[C:3]1=[O:21])=[O:12])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: COC(=O)[C@@H](N)CCCCNC(=O)OCc1ccccc1
Reactant: CN=C=S
Agent: NCCCC[C@H](N)C(=O)O
Solvent: CC#N
Product: CN1C(=O)C(CCCCNC(=O)OCc2ccccc2)NC1=S
Yield: 22.4 %

Procedure:
A solution of Nε-benzyloxycarbonyl-L-lysine methyl ester (4.66 g., 0.016 mol.) (prepared from L-lysine according to the method of Bergmann et al., J. Biol. Chem. 1935, 111, 245) in acetonitrile (20 ml.) was treated with methyl isothiocyanate (1.16 g., 0.016 mol.) and the mixture heated at reflux for 3 hours. The solvent was removed in vacuo and the residual oil triturated with ethanol to give a white solid which recrystallised from ethanol to give the title compound as colourless needles (1.2 g.) m.p. 135°C. (Found: C, 57.3; H, 6.4; N, 12.2; C16H21N3O3S requires: C, 57.3; H, 6.3; N, 12.5%).
Reaction SMILES: [OH:1][C:2]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([N+:14]([O-:16])=[O:15])=[C:8]2[C:3]=1[C:4]([CH3:17])=[CH:5][CH:6]=[N:7]2.Br[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CN(P(N(C)C)(N(C)C)=O)C.C1OC1C>CCN(CC)CC>[CH3:13][O:12][C:11]1[C:2]([O:1][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:3]2[C:8](=[C:9]([N+:14]([O-:16])=[O:15])[CH:10]=1)[N:7]=[CH:6][CH:5]=[C:4]2[CH3:17]
Reactant: COc1cc([N+](=O)[O-])c2nccc(C)c2c1O
Reactant: BrCCCCCCCCc1ccccc1
Agent: CC1CO1
Solvent: CCN(CC)CC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: COc1cc([N+](=O)[O-])c2nccc(C)c2c1OCCCCCCCCc1ccccc1
Reaction time: 1 h
Yield: 60.6 %

Procedure:
To a stirred mixture of 5-hydroxy-6-methoxy-4-methyl-8-nitroquinoline (4.98 g, 0.02 mol), 1-bromo-8-phenyloctane (4.7 g, 0.017 mol) and HMPA (13 ml), at 120° C., was added, dropwise, during 1 h, a mixture of propylene oxide (6 ml) and Et3N (1 ml). The reaction was continued for 3.5 h, allowed to cool and extracted successively with pet ether, Et2O and Me2CO leaving 1 g of insoluble starting material, 5-hydroxy-6-methoxy-4methyl-8-nitroquinoline. The combined pet ether and Et2O extracts were washed (H2O, dil NaOH, H2O), dried (Na2SO4) and concentrated. The residue was dissolved in CHCl3, placed on a silica gel column and eluted with CHCl3. Concentration of the eluates left an oil which was triturated with pet ether to give 4.35 g (60%) of 6-methoxy-4-methyl-8-nitro-5(8-phenyloctoxy) quinoline as yellow solid, mp 39.5°-41° C. Crystallization from hexane (Darco) provided the analytical sample as yellow crystals, mp 41°-42° C.
Reaction SMILES: Cl[C:2]1[S:3][C:4]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3([C:20]4=[CH:21][C:22]5[O:26][CH2:25][O:24][C:23]=5[CH:27]=[C:19]4[O:18][CH2:17]3)[C:9]2=[O:28])=[CH:5][N:6]=1.[CH3:29][NH:30][CH3:31].O1CCCC1>CN(C)C=O>[CH3:29][N:30]([CH3:31])[C:2]1[S:3][C:4]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3([C:20]4=[CH:21][C:22]5[O:26][CH2:25][O:24][C:23]=5[CH:27]=[C:19]4[O:18][CH2:17]3)[C:9]2=[O:28])=[CH:5][N:6]=1
Reactant: CNC
Reactant: O=C1N(Cc2cnc(Cl)s2)c2ccccc2C12COc1cc3c(cc12)OCO3
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CN(C)c1ncc(CN2C(=O)C3(COc4cc5c(cc43)OCO5)c3ccccc32)s1
Temperature: 120 °C
Yield: 76 %

Procedure:
To a solution of 1′-[(2-chloro-1,3-thiazol-5-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.10 g, 0.24 mmol) in N,N-dimethylformamide (5 mL) was added 2 M dimethyl amine in tetrahydrofuran (2.0 mL, 4.0 mmol) under nitrogen in a sealed tube. The reaction mixture was heated at 120° C. for 16 h. The reaction was quenched with the water, then extracted with ethyl acetate (2×50 mL). The combined organic solution was dried over sodium sulfate, filtered, and the filtrate was concentrated to dryness. The residue was purified by flash chromatography with 30% ethyl acetate in hexanes to afford 1′-{[2-(dimethylamino)-1,3-thiazol-5-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.08 g, 76%) as a colorless solid: mp 200-202° C.; 1H NMR (300 MHz, CDCl3) δ 7.27 (ddd, J=7.5, 7.5, 0.9 Hz, 1H), 7.20 (s, 1H), 7.15 (d, J=7.5 Hz, 1H), 7.08-6.95 (m, 2H), 6.51 (s, 1H), 6.14 (s, 1H), 5.91-5.84 (m, 2H), 5.05 (d, J=15.6 Hz, 1H), 4.93 (d, J=9.0 Hz, 1H), 4.84 (d, J=15.6 Hz, 1H), 4.65 (d, J=9.0 Hz, 1H), 3.06 (s, 6H); 13C NMR (75 MHz, CDCl3) δ177.2, 172.0, 156.1, 149.0, 142.5, 141.5, 139.1, 132.4, 129.1, 124.1, 123.7, 119.7, 119.5, 109.2, 103.3, 101.6, 93.7, 80.5, 58.2, 40.4, 37.2; MS (ES+) m/z 422.1 (M+1).
Reaction SMILES: C([Li])CCC.CCCCCC.C(OP([CH2:20][C:21]([CH3:28])=[CH:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])(OCC)=O)C.[CH2:29]([O:32][C:33]1[C:34](/[C:47](/[CH2:52][CH3:53])=[C:48](/[F:51])\[CH:49]=O)=[CH:35][C:36]2[C:37]([CH3:46])([CH3:45])[CH2:38][CH2:39][C:40]([CH3:44])([CH3:43])[C:41]=2[CH:42]=1)[CH2:30][CH3:31]>C1COCC1.CN1CCCN(C)C1=O>[CH2:29]([O:32][C:33]1[C:34](/[C:47](/[CH2:52][CH3:53])=[C:48](/[F:51])\[CH:49]=[CH:20]\[C:21](\[CH3:28])=[CH:22]\[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:35][C:36]2[C:37]([CH3:46])([CH3:45])[CH2:38][CH2:39][C:40]([CH3:44])([CH3:43])[C:41]=2[CH:42]=1)[CH2:30][CH3:31]
Reactant: CCOC(=O)C=C(C)CP(=O)(OCC)OCC
Reactant: CCCOc1cc2c(cc1/C(CC)=C(/F)C=O)C(C)(C)CCC2(C)C
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Product: CCCOc1cc2c(cc1/C(CC)=C(F)\C=C\C(C)=C\C(=O)OCC)C(C)(C)CCC2(C)C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of n-butyl lithium and hexane (6.75 mL, 1.6 M, 10.8 mmol) was added over 20 minutes down the side of the flask into a stirring solution of ethyl 4-(diethoxyphosphoryl)-3-methylbut-2-enoate (2.86 g, 10.8 mmol) and THF (40 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.70 mL) at −78° C. After 30 min, the solution was treated with a solution of (E)-3-(3-propoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-fluoropent-2-enal (Intermediate 9, 1.80 g, 5.42 mmol) in THF (10 mL). The solution was stirred for 2 h at 0° C. and then cooled again to −78° C. The reaction was quenched at −78° C. by adding saturated aqueous ammonium chloride. The solution was warmed to room temperature, and the products were extracted three times with ether. The combined organic layers were washed with water, brine and dried over magnesium sulfate. The solvent was removed in vacuo to give the title compound after purification by silica gel chromatography using a 94:6 mixture of hexane:ethyl acetate.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([C:9](=[O:15])[CH2:10][CH2:11][CH2:12][CH2:13][Cl:14])[CH:5]=[CH:4][C:3]=1[O:16][CH3:17].[CH3:18][N:19]([CH2:21]N(C)C)[CH3:20].C(OC(=O)C)(=O)C.[OH-].[Na+]>>[CH3:18][N:19]([CH2:21][CH:10]([CH2:11][CH2:12][CH2:13][Cl:14])[C:9]([C:6]1[CH:5]=[CH:4][C:3]([O:16][CH3:17])=[C:2]([Cl:1])[C:7]=1[Cl:8])=[O:15])[CH3:20]
Reactant: CN(C)CN(C)C
Reactant: COc1ccc(C(=O)CCCCCl)c(Cl)c1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)OC(C)=O
Product: COc1ccc(C(=O)C(CCCCl)CN(C)C)c(Cl)c1Cl
Temperature: 50 °C
Reaction time: 15 h

Procedure:
2,3-Dichloro-4-(5-chloropentanoyl)anisole (29.5 g, 0.1 mole) and N,N,N',N'-tetramethyldiaminomethane (25.5 g, 0.249 mole) were stirred and heated at 50° C. and then acetic anhydride (36.8 g, 0.36 mole) was added dropwise with stirring at such a rate that the temperature rose to 100° C. After heating at 95° C. for an additional 2 hours, the mixture was kept at ambient temperature for 15 hours, poured into crushed ice (400 g), strongly basified with 10 normal sodium hydroxide and extracted with ether. The ether extract was dried over Na2SO4 and the solvent removed in vacuo to give 2-(dimethylaminomethyl)-5-chloro-1-(2,3-dichloro-4-methoxyphenyl)-1-pentanone as a viscous oil.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([O:17][CH2:18][CH2:19]Cl)[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([O:17][CH2:18][CH2:19][N:32]3[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]3)[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN1CCNCC1
Reactant: Cc1cccc(-c2nc3ccc(OCCCl)cc3n2Cc2ccccc2)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1cccc(-c2nc3ccc(OCCN4CCN(C)CC4)cc3n2Cc2ccccc2)c1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
The title compound was prepared by reacting the compound of Example 98, supra, (1.89 g, 5.01 mmol) with 1-methyl-piperazine (65 ml) in the presence of N,N-diisopropylethyl amine (4 ml) and N,N-dimethylformamide (100 ml) under nitrogen atmosphere. This reaction mixture was heated to 50° C. and stirred overnight at that temperature. The compound was purified essentially as described in Example 99, supra. NMR, IR, MS 440, 441, mp 91° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@@H:12](O)[CH3:13])[CH2:11][O:10]1.[NH:15]1[CH:19]=[CH:18][N:17]=[N:16]1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@H:12]([N:16]2[N:17]=[CH:18][CH:19]=[N:15]2)[CH3:13])[CH2:11][O:10]1
Reactant: C[C@H](O)[C@@]1(c2ccc(F)cc2F)CO1
Reactant: c1c[nH]nn1
Product: C[C@@H](n1nccn1)[C@@]1(c2ccc(F)cc2F)CO1

Procedure:
Using (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (202 mg) and 1H-1,2,3-triazole (0.17 ml), (2S)-2-(2,4-difluorophenyl)-2-[(1R)-1-(2H-1,2,3-triazol-2-yl) ethyl]oxirane (172 mg) was obtained by the same way as in Reference Example 10.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C@H:10]1[CH2:15][CH2:14][C@H:13]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][CH2:23][CH:24]=[O:25])[CH2:18][CH2:17]2)[CH2:12][CH2:11]1)[CH2:8][CH3:9].[OH-].[Na+]>C1COCC1>[CH2:7]([C@H:10]1[CH2:15][CH2:14][C@H:13]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][CH2:23][CH2:24][OH:25])[CH2:18][CH2:17]2)[CH2:12][CH2:11]1)[CH2:8][CH3:9]
Reactant: CCC[C@H]1CC[C@H]([C@H]2CC[C@H](CCC=O)CC2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC[C@H]1CC[C@H]([C@H]2CC[C@H](CCCO)CC2)CC1

Procedure:
Under a nitrogen gas stream, 200 ml of THF was cooled to 5° C. or less on an ice bath, and 4.31 g (113 mmol) of lithium aluminum hydride was then added, followed by stirring. Next, 200 ml of a THF solution containing 40.0 g (151 mmol) of crude 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propanal obtained in the third step of Example 2 was added dropwise, while the same temperature was kept, followed by stirring at room temperature for 6 hours. The reaction mixture was slowly added to 50 ml of a 2N aqueous sodium hydroxide solution, and then stirred at 50° C. for 30 minutes. The reaction mixture was filtered through Celite, and the solvent was then distilled off under reduced pressure, followed by extraction with ethyl acetate. Afterward, the extract was dried over anhydrous magnesium sulfate. Next, the solvent was distilled off under reduced pressure to obtain 34.0 g of crude 3-(trans-4-(trans-4-propylcyclohexyl)cyclohexyl)propanol.
Reaction SMILES: O=C1C2C(=CC=CC=2)C2CC3C(C(O)=O)=CC=CC=3C=2N1.[O:22]=[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]2[CH2:33][C:34]3[CH:35]=[C:36]([C:40]([O:42]C)=[O:41])[CH:37]=[CH:38][C:39]=3[C:25]=2[NH:24]1>>[O:22]=[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]2[CH2:33][C:34]3[CH:35]=[C:36]([C:40]([OH:42])=[O:41])[CH:37]=[CH:38][C:39]=3[C:25]=2[NH:24]1
Reactant: COC(=O)c1ccc2c(c1)Cc1c-2[nH]c(=O)c2ccccc12
Agent: O=C(O)c1cccc2c1Cc1c-2[nH]c(=O)c2ccccc12
Product: O=C(O)c1ccc2c(c1)Cc1c-2[nH]c(=O)c2ccccc12

Procedure:
The above compound was made according to the procedure for preparing 5,6-dihydro-5-oxo-11-H-indeno[1,2-c]isoquinoline-10-carboxylic acid (18b), but using Compound 18a in place of Compound 17a. 1H NMR (DMSO-d6): δ 12.34 (s, 1H); 8.24 (d, J=8.1 Hz, 1H); 8.20 (d, J=7.5 Hz 1H); 7.88 (d, J=7.8 Hz, 1H); 7.77 (m, 2H); 7.54 (d, J=7.8 Hz, 2H); 7.49 (d, J=8.1 Hz, 1H); 4.18 (s, 2H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[CH2:11][CH2:10][CH2:9][C:8]2=O)[CH:2]=1.Cl.[CH2:14]([O:21][NH2:22])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>N1C=CC=CC=1>[CH2:14]([O:21][N:22]=[C:8]1[CH2:9][CH2:10][CH2:11][CH:7]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NOCc1ccccc1
Reactant: O=C1CCCC1c1cccnc1
Agent: Cl
Solvent: c1ccncc1
Product: c1ccc(CON=C2CCCC2c2cccnc2)cc1
Temperature: 60 °C
Reaction time: 4.5 h

Procedure:
A mixture of (±)-2-(3-pyridyl)cyclopentanone (2.0 g) and benzyloxyamine hydrochloride (1.98 g) in anhydrous pyridine was stirred at 60° C. for 4.5 hours. The pyridine was removed in vacuo (40° C., 0.2 mmHg), the residue was dissolved in chloroform (75 ml), washed with water (4×75 ml), dried over magnesium sulphate and evaporated. The residual oil was purified by flash chromatography on silica, eluting with chloroform/methanol (100/1) to give (±)-2-benzyloxyimino -1-(3-pyridyl)cyclopentane (mixture of syn and anti isomers, 1:3), a pale yellow oil (2.91 g).
Reaction SMILES: [NH2:1][C@H:2]([CH2:5][S:6][C:7]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][OH:4].C(N(CC)CC)C.[C:33]([C:41]1[C:42](=[O:52])[N:43]([CH3:51])[C:44](=[O:50])[N:45]([CH3:49])[C:46]=1[CH2:47]Br)(=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CCO>[OH:4][CH2:3][C@H:2]([N:1]1[C:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[C:41]2[C:46]([N:45]([CH3:49])[C:44](=[O:50])[N:43]([CH3:51])[C:42]2=[O:52])=[CH:47]1)[CH2:5][S:6][C:7]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: N[C@@H](CO)CSC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cn1c(CBr)c(C(=O)c2ccccc2)c(=O)n(C)c1=O
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cn1c(=O)c2c(-c3ccccc3)n([C@@H](CO)CSC(c3ccccc3)(c3ccccc3)c3ccccc3)cc2n(C)c1=O
Temperature: 25 °C

Procedure:
(S)-2-Amino-3-(tritylthio)propan-1-ol (step 1) (1.58 g, 4.52 mmol), triethylamine (1.454 mL, 10.43 mmol) and 5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (Intermediate C) (1.173 g, 3.48 mmol) were combined in EtOH (60 mL) and the mixture heated at reflux for 1 hour. The reaction mixture was cooled to RT and evaporated under vacuum. The residue was partitioned between DCM and water and the phases separated. The organic phase was passed through a hydrophobic frit and evaporated under vacuum to give the title compound which was used without further purification.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][C:5](=[O:10])[CH2:6][CH2:7][CH2:8][CH3:9]>[Ru].[Fe].[Ni].[Pd]>[CH3:1][CH2:2][CH2:3][CH2:4][CH:5]([OH:10])[CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCC(=O)CCCC
Agent: [Fe]
Agent: [Ni]
Agent: [Pd]
Product: CCCCC(O)CCCC

Procedure:
Diesel fuels by hydrogenation combined with dehydration over a bi-functional catalyst containing metal (e.g., Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, Pt, Ag, Au, and combinations thereof) and acid sites (e.g., silica-alumina, etc.) (Huber (2007), West (2008)). Alternatively, the stream of 5-nonanone can undergo hydrogenation over a Ru/C catalyst operating at 423 K to produce 5-nonanol, followed by dehydration over an acid catalyst at 423 K (e.g., ZSM-5) to produce nonene. Importantly, all of these C9 compounds spontaneously separate from water. The water may then be recycled back to the GVL stream entering the reactor containing the Pd/niobia catalyst. The liquid stream of linear nonene undergoes isomerization over a zeolite catalyst (e.g., ZSM-5 at 523 K) to produce branched C9-olefins (or alkanes upon subsequent hydrogenation) for use as gasoline components. Alternatively, nonene undergoes dimerization over an acid catalyst (e.g., “AMBERLYST”-brand catalysts at 433 K) to produce a mixture of C9 and C18 olefins (or alkanes upon subsequent hydrogenation) for use in jet and Diesel fuels. (“AMBERLYST” is a registered trademark of Rohm & Haas Company, a wholly owned subsidiary of Dow Chemical Company.)
Reaction SMILES: [Cl:1][C:2]1[CH:32]=[CH:31][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:18]=3)[CH2:15][NH2:16])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[C:41](Cl)([O:43]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:14]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH:18]=4)[CH2:15][NH:16][C:41]3=[O:43])=[CH:9][CH:8]=2)=[CH:31][CH:32]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: NCC(Nc1ccc(Oc2ccc(Cl)cc2)cc1)c1cccc(OCc2ccccc2)c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1NCC(c2cccc(OCc3ccccc3)c2)N1c1ccc(Oc2ccc(Cl)cc2)cc1
Yield: 98.7 %

Procedure:
To the diamine (440 mg, 0.98 mmol) from Step 2, and triethylamine (330 μL, 2.4 mmol) in THF (20 mL) is added triphosgene (180 mg, 0.6 mmol) in THF at 0° C. After complete addition, the mixture is quenched with water and THF is removed by evaporation. The residue is extracted with ethyl acetate and washed with water. Evaporation of the organics gives a solid which is triturated with ethyl acetate, filtered, and washed with 40% ethyl acetate/hexane to give 279 mg of the title compound. Purification of the filtrate gives an additional 127 mg of product (combined yield, 88%). HPLC-MS calculated for C28H23ClN2O3 (M+H+): 471.1, found 471.1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]4)[C:14]([F:31])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.C[O-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:19]4)[C:14]([F:31])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3ncc(F)c(N[C@H]4CCCN(C(=O)OC(C)(C)C)C4)n3)c3cc(Cl)cnc32)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC[C@H](Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)C1
Temperature: 45 °C
Reaction time: 0.5 h

Procedure:
To a solution of tert-butyl (3S)-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]piperidine-1-carboxylate, 1b, (0.93 g, 1.55 mmol) in methanol (10 mL) was added sodium methoxide (10 mL of 1M solution). The reaction mixture was warmed to 45° C. After stirring for 30 minutes the reaction was to cooled to room temperature and quenched by addition into water. The mixture was diluted with EtOAc and the layers were separated. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (0-100% EtOAc/Hexanes) to afford the desired product, 2b.