Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:22]=[C:21]([CH3:23])[C:20]([NH2:24])=[C:19]([CH3:25])[CH:18]=2)[CH:13]=[CH:12][C:11]=1[N+:26]([O-:28])=[O:27])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]([O:33][C:34](=O)[O:35]C(C)(C)C)([CH3:32])([CH3:31])[CH3:30].C(N(CC)CC)C>O1CCCC1>[C:1]([O:5][C:6]([N:8]([C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:18]=[C:19]([CH3:25])[C:20]([NH:24][C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:35])=[C:21]([CH3:23])[CH:22]=2)[CH:13]=[CH:12][C:11]=1[N+:26]([O-:28])=[O:27])[CH3:9])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Reactant: Cc1cc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc(C)c1N
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1cc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc(C)c1NC(=O)OC(C)(C)C
Yield: 60.9 %

Procedure:
A mixture of 2-(N-t-butoxycarbonyl-N-methylamino)-4-(4-amino-3,5-dimethylphenoxy)nitrobenzene (2.27 g), di-t-butylcarbonate (1.28 g),triethylamine (0.59 g) and anhydrous tetrahydrofuran (20 ml) was heated at reflux for 6 hours. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column using hexane: ethyl acetate=10:1 as the eluant to afford the title compound (1.74 g, mp 154-156° C. ).
Reaction SMILES: [OH:1][CH2:2][C:3]1O[CH:5]=[C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:7](=[O:9])[CH:8]=1.Cl.[NH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O>[OH:1][CH2:2][C:3]1[N:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:5]=[C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:7](=[O:9])[CH:8]=1
Reactant: Nc1ccccc1
Reactant: CCCCCCCCCCCCCCCCCCOc1coc(CO)cc1=O
Agent: Cl
Solvent: O
Product: CCCCCCCCCCCCCCCCCCOc1cn(-c2ccccc2)c(CO)cc1=O

Procedure:
5.0 g (12 mMole) 2-hydroxymethyl-5 octadecyloxy-4-pyranone are suspended in 90 mL water and 2 mL concentrated hydrochloric acid and mixed with 4.0 g (43 mMole) aniline. The mixture is heated under reflux for 24 hours, cooled and the precipitate formed is separated from the aqueous solution and recrystallized from ethyl acetate, an almost colorless product being obtained; m.p. 67°-72° C. In a manner analogous to that described in Example 30, there is obtained the following compound:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11](/[CH:22]=[CH:23]/[C:24]([O:26][CH3:27])=[O:25])[CH:12]=[N:13][C:14]=1[NH:15][C:16]1[S:17][CH:18]=[C:19]([CH3:21])[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1C=CC(S(NN)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])[CH:12]=[N:13][C:14]=1[NH:15][C:16]1[S:17][CH:18]=[C:19]([CH3:21])[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)/C=C/c1cnc(Nc2nc(C)cs2)c(OCc2ccccc2)c1
Agent: Cc1ccc(S(=O)(=O)NN)cc1
Solvent: Cc1ccccc1
Product: COC(=O)CCc1cnc(Nc2nc(C)cs2)c(OCc2ccccc2)c1
Yield: 32.3 %

Procedure:
A 25 mL round-bottomed flask was charged with (E)-methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-yl)acrylate (430 mg, 1.13 mmol), 4-methylbenzenesulfonohydrazide (1050 mg, 5.64 mmol) and toluene (10 mL). The reaction was heated to reflux for 12 hours. The reaction was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (20% EtOAc in hexanes) to afford the title compound (140 mg, 32.4% yield) as a white solid. 1H NMR (CDCl3) δ 8.49 (s, 1H), 7.80 (d, 1H), 7.41 (m, 5H), 7.00 (d, 1H), 6.37 (q, 1H), 5.08 (s, 2H), 3.67 (s, 3H), 2.89 (t, 2H), 2.61 (t, 2H), 2.31 (d, 3H). Mass spectrum (apci) m/z=384.1 (M+H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2.[H-].[Na+].[Cl:15][C:16]1[C:21]([O:22][CH2:23][O:24][CH3:25])=[CH:20][CH:19]=[C:18]([Cl:26])[C:17]=1[CH2:27]OS(C)(=O)=O.O>CN(C)C=O>[Cl:15][C:16]1[C:21]([O:22][CH2:23][O:24][CH3:25])=[CH:20][CH:19]=[C:18]([Cl:26])[C:17]=1[CH2:27][O:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2
Reactant: COCOc1ccc(Cl)c(COS(C)(=O)=O)c1Cl
Reactant: Cc1ccc2cccc(O)c2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCOc1ccc(Cl)c(COc2cccc3ccc(C)nc23)c1Cl
Reaction time: 1 h

Procedure:
A solution of 8-hydroxy-2-methylquinoline (737 mg) in dimethylformamide was dropwise added to a solution of sodium hydride (60% in oil, 185 mg) in dimethylformamide under ice-bath cooling, and the mixture was stirred for 1 hour at the same temperature. To the mixture was added 2,6-dichloro-1-methylsulfonyloxymethyl-3-(methoxymethoxy)benzene (1.46 g) under ice-bath cooling, and the mixture was stirred for 1 hour at the same temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate-n-hexane) to give 8-[2,6-dichloro-3-(methoxymethoxy)-benzyloxy]-2-methylquinoline as an oil.
Reaction SMILES: [CH3:1][C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH3:11].[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][CH:23]=1)[C:17](=[O:20])[CH2:18]Br.Br>>[CH3:1][C:2]1[N:10]=[C:5]2[N:6]([CH2:18][C:17]([C:16]3[CH:21]=[CH:22][CH:23]=[C:14]([O:13][CH3:12])[CH:15]=3)=[O:20])[CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH3:11]
Reactant: Cc1[nH]c2ncccc2c1C
Reactant: COc1cccc(C(=O)CBr)c1
Agent: Br
Product: COc1cccc(C(=O)Cn2cccc3c(C)c(C)nc2-3)c1

Procedure:
The title compound was prepared on a 0.9 mmol scale fr 2,3-dimethylpyrrolo[2,3-b]pyridine and m-methoxyphenacyl bromide in the same manner as described in example 27 giving 228 mg (70%) pure product as the hydrobromide.
Reaction SMILES: C(N(CC)CC)C.Cl.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:20][CH2:19][NH:18][CH2:17]2)=[CH:12][CH:11]=1.Cl[C:22]([O:24][CH3:25])=[O:23]>C1COCC1.O>[Br:9][C:10]1[CH:11]=[CH:12][C:13]([CH:16]2[CH2:20][CH2:19][N:18]([C:22]([O:24][CH3:25])=[O:23])[CH2:17]2)=[CH:14][CH:15]=1
Reactant: COC(=O)Cl
Reactant: Brc1ccc(C2CCNC2)cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)N1CCC(c2ccc(Br)cc2)C1
Reaction time: 0.08 h
Yield: 111.1 %

Procedure:
Triethylamine (192 mg, 1.9 mmol) was added to a suspension of 3-(4-bromophenyl)pyrrolidine hydrochloride (200 mg, 0.76 mmol) in anhydrous THF (5 mL). The reaction mixture was stirred for 5 minutes and treated with methyl chloroformate (0.1 g, 1.05 mmol). The reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was diluted with water and extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give methyl 3-(4-bromophenyl)pyrrolidine-1-carboxylate (0.24 g, quantitative yield) as an oil which was used for next step directly. MS (ES+) 283.9 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH:3]1[CH2:7][O:6][C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20](=[O:24])[CH2:21][C:22]#[N:23])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:4]1.CO[CH:27](OC)[N:28]([CH3:30])[CH3:29]>>[Cl:1][CH2:2][CH:3]1[CH2:7][O:6][C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20](=[O:24])[C:21](=[CH:27][N:28]([CH3:30])[CH3:29])[C:22]#[N:23])([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[O:4]1
Reactant: N#CCC(=O)c1ccccc1C1(c2ccccc2)OCC(CCl)O1
Reactant: COC(OC)N(C)C
Product: CN(C)C=C(C#N)C(=O)c1ccccc1C1(c2ccccc2)OCC(CCl)O1
Reaction time: 1.5 h

Procedure:
A solution of 20 g (0.0585 mol) of the above propanenitrile in 75 ml of N,N-dimethylformamide dimethylacetal was refluxed and stirred for 90 mins, and evaporated to dryness. The oil was triturated with ice water which was decanted, and the residue was partitioned between 150 ml of dichloromethane and 150 ml of water. The organic layer was dried with sodium sulfate, concentrated, and filtered through 150 g of Florisil. The column was eluted with ether which was evaporated, and the resulting oil was crystallized from ethanol to give end product. A sample was recrystallized from dichloromethane/ether to give white prisms, mp 107°-110° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH:20]3[CH2:21][CH:22]([C:24]4[O:28][N:27]=[C:26]([CH3:29])[N:25]=4)[CH2:23][CH:12]2[CH2:13][C:14]2([CH2:19]3)OCC[O:15]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl>O1CCOCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]2[CH:12]3[CH2:23][CH:22]([C:24]4[O:28][N:27]=[C:26]([CH3:29])[N:25]=4)[CH2:21][CH:20]2[CH2:19][C:14](=[O:15])[CH2:13]3)(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: Cc1noc(C2CC3CC4(CC(C2)N3S(=O)(=O)c2ccc(Cl)cc2)OCCO4)n1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Cc1noc(C2CC3CC(=O)CC(C2)N3S(=O)(=O)c2ccc(Cl)cc2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
9-[(4-Chlorophenyl)sulfonyl]-7-(3-methyl-1,2,4-oxadiazol-5-yl)spiro[9-azabicyclo[3.3.1]nonane-3,2′-[1,3]dioxolane] (51) (0.40 g, 0.916 mmol) was covered with HCl in dioxane (4 N, 2 mL). The reaction mixture was stirred at room temperature for 2 h after which it was diluted with EtOAc and washed with aqueous sodium hydroxide (1 N). The organic phase was dried (Na2SO4), filtered and concentrated under vacuum to yield 0.36 g (quant.) of 9-[(4-chlorophenyl)sulfonyl]-7-(3-methyl-1,2,4-oxadiazol-5-yl)-9-azabicyclo[3.3.1]nonan-3-one (52). MS (ESI) 396.1 (M+H).
Reaction SMILES: C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:28])[C:14]=1[C:15]1[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][CH:20]=1>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:28])[C:14]=1[C:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2c(F)cncc2Cl)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Fc1cncc(Cl)c1C1=CCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.2 %

Procedure:
TFA (2 mL, 25.96 mmol) was added to a stirred solution of tert-butyl 4-(3-chloro-5-fluoro-4-pyridyl)-3,6-dihydro-2H-pyridine-1-carboxylate (708 mg, 2.264 mmol) in DCM (10 mL) and the reaction stirred at ambient temperature for 2 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The residue was passed through a 10 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures and concentrated in vacuo to give 3′-chloro-5′-fluoro-1,2,3,6-tetrahydro-4,4′-bipyridine as an off-white solid (468 mg, 97% Yield). MS (ES+) 213.1.
Reaction SMILES: [Na].[CH3:2][O:3][C:4]1[N:9]=[CH:8][C:7]2[CH:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[C:11](=O)[CH2:12][CH2:13][CH2:14][C:6]=2[CH:5]=1.[O-]CC.[Na+].[CH3:27][C:28](=[O:31])[CH:29]=[CH2:30]>CCO>[CH3:2][O:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]3([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[CH2:30][CH2:29][C:28](=[O:31])[CH:27]=[C:11]3[CH2:12][CH2:13][CH2:14][C:6]=2[CH:5]=1
Reactant: C=CC(C)=O
Reactant: COc1cc2c(cn1)C(Cc1ccccn1)C(=O)CCC2
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: COc1cc2c(cn1)C1(Cc3ccccn3)CCC(=O)C=C1CCC2
Temperature: 63 °C
Reaction time: 0.75 h
Yield: 60.1 %

Procedure:
Sodium (2.21 g, 96 mmol) and EtOH (350 mL) were stirred until a solution was formed. 3-Methoxy-9-(pyridin-2-ylmethyl)-6,7-dihydro-5H-cyclohepta[c]pyridin-8 (9H)-one (128, R2=Pyridin-2-ylmethyl) (26.6 g, 94 mmol) was suspended in EtOH (220 mL) then treated with the sodium ethoxide solution. The mixture was warmed to an internal temperature of about 63° C. then but-3-en-2-one (9.76 mL, 118 mmol) was added over about 2 to 3 min. The mixture was stirred at an internal temperature of about 65-70° C. for about 45 min then the mixture was cooled to rt. The solvents were removed under reduced pressure then the material was stirred with EtOH (250 mL) for about 30 min. The solids were collected by filtration then washed with EtOH (25 mL). The material was dried to yield 3-methoxy-11a-(pyridin-2-ylmethyl)-6,7,11,11a-tetrahydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridin-9(10H)-one (129, R2=Pyridin-2-ylmethyl) (18.89 g, 60.0%); LC/MS, method 3, Rt=1.12, 1.82 min, MS m/z 335 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.44 (s, 1H), 8.42-8.37 (m, 1H), 7.63-7.58 (m, 1H), 7.18-7.14 (m, 1H), 7.13-7.08 (m, 1H), 6.58 (s, 1H), 5.88 (s, 1H), 3.83 (s, 3H), 3.70 (d, J=13.4 Hz, 1H), 3.56 (d, J=13.4 Hz, 1H), 2.87-2.75 (m, 1H), 2.74-2.59 (m, 2H), 2.41-2.05 (m, 4H), 1.85-1.65 (m, 3H).
Reaction SMILES: [CH3:1][OH:2].[H-].[Na+].[CH:5]([N:9]=[N:10][C:11]([N:17]=[C:18]=[O:19])([CH2:13][CH:14]([CH3:16])[CH3:15])[CH3:12])([CH2:7][CH3:8])[CH3:6]>O>[CH:5]([N:9]=[N:10][C:11]([NH:17][C:18]([O:2][CH3:1])=[O:19])([CH2:13][CH:14]([CH3:15])[CH3:16])[CH3:12])([CH2:7][CH3:8])[CH3:6]
Reactant: CCC(C)N=NC(C)(CC(C)C)N=C=O
Reactant: CO
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CCC(C)N=NC(C)(CC(C)C)NC(=O)OC
Temperature: 25 °C

Procedure:
To 25 ml of stirred methanol in a 125 ml erlenmeyer flask was slowly added 1.2 grams (0.028 moles) of 57% sodium hydride. The solution was cooled to 25° C in a cold water bath and 5.9 grams (.028 moles) of 2-sec.-butylazo-2-isocyanato-4-methylpentane (from Example XVII) was added dropwise over 5 minutes. The reaction was stirred an additional hour at room temperature, poured into 200 ml water, the product extracted with 100 ml pentane, washed with 100 ml saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered and the pentane evaporated under reduced pressure on a rotating evaporator. The product was a yellow liquid and weighed 3.9 grams (57.3% crude yield). The infrared spectrum was in agreement with the structure of 2-sec-butylazo-2-(methoxycarbonylamino)-4-methylpentane (strong carbonyl band at 1740 cm-1, sharp NH at 3375 cm-1 and no isocyanate band at 2125-2225 cm-1).
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[C:12]([CH2:15]OS(C)(=O)=O)=[CH:11][C:10]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([CH3:28])[CH:22]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][NH:30][CH3:31]>>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([CH2:15][N:30]([CH3:31])[CH3:29])=[CH:11][C:10]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([CH3:28])[CH:22]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CNC
Reactant: Cc1cc(-c2cc(COS(C)(=O)=O)c(=O)n(Cc3ccccc3)n2)ccc1F
Product: Cc1cc(-c2cc(CN(C)C)c(=O)n(Cc3ccccc3)n2)ccc1F
Yield: 92.7 %

Procedure:
Following the procedure of Example 7, 2-benzyl-6-(4-fluoro-3-methylphenyl)-4-methanesulfonyloxymethyl-2H-pyridazin-3-one and dimethylamine were reacted to yield the title compound as a yellow oil (yield: 92.7%).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([CH3:23])=[O:22].Cl.CN[OH:27].C(N(CC)CC)C>CO>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:15])([F:16])[F:17])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([CH:19]=[N:20][OH:27])[C:3]=1[S:21]([CH3:23])=[O:22]
Reactant: CNO
Reactant: CS(=O)c1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: CS(=O)c1c(C=NO)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N

Procedure:
A mixture of 5-amino-3-cyano 1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-methylsulfinyl-1H-pyrazole (1g), methylhydroxylamine hydrochloride (0.26g) and triethylamine (0.4g) was stirred in methanol at ambient temperature for 2 hours, evaporated, washed (water) extracted with ethyl acetate to give 5-amino- 1-[2,6-dichloro4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime (0.35g) as a white solid m.p. about 190° C.
Reaction SMILES: [CH2:1]([CH:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:10][OH:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].CC(C)=[O:24].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[CH2:1]([CH:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:10]([OH:24])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CC(C)=O
Reactant: CCCCCCCCCCC(CO)CCCCCCCC
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CCCCCCCCCCC(CCCCCCCC)C(=O)O

Procedure:
To the reactor as in Example 1, decanol-1 (300 g) was charged to the reactor and ZnO (2 g), KOH (6 g), CaO (5 g) and Cu Bronze (1.5 g) were added. The above reaction mixture was heated at 200° C. for 6 h to complete the reaction. The reaction mixture was filtered and purified by distillation to get 2-octyl-1-dodecanol (250 g). 2-octyl-1-dodecanol (250 g) was reacted with Jones reagent (200 ml) in acetone (200 ml) to get 2-octyl-1-dodecanoic acid. 2-Octyl-1-dodecanoic acid (200 g) was again charged to the reactor and subsequently, methanol (200 g) and sulfuric acid (6.0 g) were added slowly to the reactor with stirring. The reaction mixture was refluxed till completion of the reaction. The reaction mixture was passed through basic alumina to get rid of residual catalyst. The catalyst free mixture was fractionated to separate un-reacted methanol and synthetic diesel. Prepared synthetic diesel was evaluated for fuel properties and results were tabulated.
Reaction SMILES: [CH:1]1([N:4]([CH2:28][C:29]2[CH:34]=[C:33]([CH2:35][CH2:36][CH2:37][C:38](OC)=[O:39])[CH:32]=[C:31]([Cl:42])[C:30]=2[Cl:43])[C:5]([C@H:7]2[C@H:12]([C:13]3[CH:18]=[CH:17][N:16]([CH3:19])[C:15](=[O:20])[CH:14]=3)[CH2:11][CH2:10][N:9]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.[BH4-].[Li+]>C1COCC1>[CH:1]1([N:4]([CH2:28][C:29]2[CH:34]=[C:33]([CH2:35][CH2:36][CH2:37][CH2:38][OH:39])[CH:32]=[C:31]([Cl:42])[C:30]=2[Cl:43])[C:5]([C@H:7]2[C@H:12]([C:13]3[CH:18]=[CH:17][N:16]([CH3:19])[C:15](=[O:20])[CH:14]=3)[CH2:11][CH2:10][N:9]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:8]2)=[O:6])[CH2:2][CH2:3]1
Reactant: COC(=O)CCCc1cc(Cl)c(Cl)c(CN(C(=O)[C@@H]2CN(C(=O)OC(C)(C)C)CC[C@H]2c2ccn(C)c(=O)c2)C2CC2)c1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cn1ccc([C@@H]2CCN(C(=O)OC(C)(C)C)C[C@H]2C(=O)N(Cc2cc(CCCCO)cc(Cl)c2Cl)C2CC2)cc1=O
Reaction time: 3 h

Procedure:
To a THF solution (0.08 M) of trans-1,1-dimethylethyl 3-{[cyclopropyl({2,3-dichloro-5-[4-(methyloxy)-4-oxobutyl]phenyl}methyl)amino]carbonyl}-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1 eq.) from the previous step was added lithium borohydride (6 eq.) in one rapid portion. After 3 h, the reaction was quenched with the careful addition of 10% aq. HCl. The aqueous layer was separated and back-extracted with EtOAc. The combined organic extract were washed further with 1 N aq. NaOH, water and brine, dried over Na2SO4 and filtered. Concentration of the filtrate in vacuo afforded the title compound as a white froth.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][C:8]([NH:16][CH3:17])=[CH:9][CH:10]=3)[C:5](=[O:18])[C:4]=2[CH:3]=1.C(N(CC)CC)C.[CH3:26][O:27][C:28]([C:30]1[CH:31]=[CH:32][C:33]2[C:37]([Cl:38])=[C:36]([C:39](Cl)=[O:40])[S:35][C:34]=2[CH:42]=1)=[O:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:26][O:27][C:28]([C:30]1[CH:31]=[CH:32][C:33]2[C:37]([Cl:38])=[C:36]([C:39](=[O:40])[N:16]([C:8]3[CH:9]=[CH:10][C:11]4[S:12][C:13]5[C:4](=[CH:3][C:2]([Br:1])=[CH:15][CH:14]=5)[C:5](=[O:18])[C:6]=4[CH:7]=3)[CH3:17])[S:35][C:34]=2[CH:42]=1)=[O:29]
Reactant: CNc1ccc2sc3ccc(Br)cc3c(=O)c2c1
Reactant: COC(=O)c1ccc2c(Cl)c(C(=O)Cl)sc2c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc2c(Cl)c(C(=O)N(C)c3ccc4sc5ccc(Br)cc5c(=O)c4c3)sc2c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 60 %

Procedure:
To 0.51 g (1.6 mmol) of 2-bromo-7-methylamino-thioxanthen-9-one (14) and 10 mL of triethylamine in 15 mL of anhyd CH2Cl2 was added 0.61 g (2.1 mmol) of 3-chloro-2-chlorocarbonyl-benzo[b]thiophene-6-carboxylic acid methyl ester (12) dissolved in 10 mL of anhyd CH2Cl2 at 5-8° C. in an ice bath. A catalytic amount of DMAP was added. The reaction mixture was warmed at room temperature and stirred for 48 h under N2. The reaction mixture was filtered to remove triethylamine hydrochloride salt, the filtrate was washed three times with aq saturated NaHCO3, H2O, three times with aq. 2N HCl to remove unreacted amines, H2O, brine, dried over Na2SO4, and concentrated in vacuo to give crude ester 10. The crude ester 10 was chromatographed on silica gel, eluting with 20% ethyl acetate in hexane to give 0.55 g (60% yield) of NMR pure 10 (LG−=Cl−) as a brown powder, mp 237-239° C. Found: C, 52.09; H, 2.64; N, 2.47%; calcd for C25H15NO4S2ClBr: C, 52.40; H, 2.62; N, 2.44%; 1H-NMR (400 MHz, CDCl3): 3.61 (3H, s), 3.92 (3H, s), 7.35-7.54 (3H, m), 7.66-7.80 (2H, m), 8.02 (1H, d, J=8.2 Hz), 8.40 (1H, s), 8.51 (1H, s), 8.69 (1H, s); 13C-NMR (100 MHz, CDCl3): 38.3, 52.6, 120.8, 120.9, 122.8, 124.9, 126.3, 127.3, 127.4, 127.8, 128.6, 129.6, 130.0, 131.0, 132.7, 134.1, 135.8, 136.1, 137.6, 138.7, 141.4, 162.5, 166.5, 178.1.
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:18][C:19]([OH:21])=[O:20]>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][CH2:18][C:19]([OH:21])=[O:20])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: O=C(O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(OCC(=O)O)CC1
Reaction time: 0.25 h

Procedure:
Sodium hydride (596 mg of a 60% dispersion in oil, 14.9 mmol) was added portionwise to a stirred solution of tert-butyl-4-hydroxypiperidine-1-carboxylate (1.0 g, 5 mmol) in anhydrous THF (20 ml) at rt. After 15 min, bromoacetic acid (1.38 g, 9.94 mmol) was introduced and stirring continued for 5 h. Additional bromoacetic acid (5 mmol) and sodium hydride (5 mmol) were added and stirring continued for 24 h. The reaction was quenched with water (2 ml) and diluted with EtOAc (20 ml), which was washed with saturated aqueous NaHCO3 (20 ml). Using dilute HCl, the aqueous phase was acidified to pH 2 and the precipitate extracted into EtOAc (50 ml). The organic phase was dried (MgSO4), evaporated and the residue was purified by flash chromatography (5% AcOH in IH-EtOAc, 7:3 to 1:1) to afford the title acid: RT=2.89 min; m/z (ES+)=260.3 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH2:14]1[C:23]2[C:18](=[C:19]([NH:24][C:25](=[O:27])[CH3:26])[CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][NH:15]1>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:15]3[CH2:16][CH2:17][C:18]4[C:23](=[CH:22][CH:21]=[CH:20][C:19]=4[NH:24][C:25](=[O:27])[CH3:26])[CH2:14]3)=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Cl)cn2n1
Reactant: CC(=O)Nc1cccc2c1CCNC2
Product: CC(=O)Nc1cccc2c1CCN(C(=O)c1cc3ncc(Cl)cn3n1)C2

Procedure:
In close analogy to the procedure described in Example 1, 6-chloro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with N-(1,2,3,4-Tetrahydro-isoquinolin-5-yl)-acetamide to provide the title compound in moderate yield.