Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1]Cl.[F:3][C:4]([F:15])([F:14])[C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[CH:7]([Cl:9])[Cl:8].II>>[F:3][C:4]([F:14])([F:15])[C:5]1[CH:13]=[C:12]([Cl:1])[CH:11]=[CH:10][C:6]=1[CH:7]([Cl:9])[Cl:8]
Reactant: FC(F)(F)c1ccccc1C(Cl)Cl
Reactant: ClCl
Agent: II
Product: FC(F)(F)c1cc(Cl)ccc1C(Cl)Cl
Temperature: 60 °C
Reaction time: 5 h

Procedure:
A 500-ml four-necked round bottom flask equipped with thermometer, mechanical stirrer, Dimroth condenser and chlorine-introducing tube was charged with 570.0 g (2.5 mol) of o-trifluoromethylbenzalchloride, 11.5 g (2.5 mol %) of ferric chloride and 1.5 g (0.5 mol %) of iodine. Then, the reaction temperature was raised to 60° C. while the mixture was kept stirred. When the reaction temperature reached 60° C., chlorination was started by continuously introducing chlorine at a rate of 0.5 mol/hr. After the lapse of 2 hr, the reaction temperature was raised to 80° C., and then the reaction was continued for another 5 hr. After the 7-hr reaction, conversion was 97.0%. Then, the reaction liquid was put into a 1000-ml separating funnel, and washed two times with 500 ml of water. The mixed liquid was allowed to separate into two layers and the aqueous layer was removed. The organic phase was dried with magnesium sulfate, and then magnesium sulfate was removed by vacuum filtration. As the result, 634.2 g of 2-trifluoromethyl-4-chlorobenzalchloride (purity: 72.1%) was obtained. The yield of this product was 69.4%. The product was analyzed by gas chromatography, and the result is as follows.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[O:10].[Br:11]Br>C(Cl)Cl>[Br:11][C:7]1[CH:8]=[CH:9][C:4]2[NH:3][C:2](=[O:10])[O:1][C:5]=2[CH:6]=1
Reactant: BrBr
Reactant: O=c1[nH]c2ccccc2o1
Solvent: ClCCl
Product: O=c1[nH]c2ccc(Br)cc2o1
Reaction time: 19.5 h

Procedure:
To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stifling at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33% of its original volume and filtered and washed as before. The combined solids weighed 28.36 g and contained ca. 8-9% starting material.
Reaction SMILES: Cl[C:2]1[C:3](=[O:19])[N:4]([CH2:15][CH2:16][O:17][CH3:18])[S:5](=[O:14])(=[O:13])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH:20]1([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>>[CH:20]1([C:26]2[CH:27]=[CH:28][C:29]([NH:30][C:2]3[C:3](=[O:19])[N:4]([CH2:15][CH2:16][O:17][CH3:18])[S:5](=[O:14])(=[O:13])[C:6]=3[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[CH:31][CH:32]=2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
Reactant: COCCN1C(=O)C(Cl)=C(c2ccccc2)S1(=O)=O
Reactant: Nc1ccc(C2CCCCC2)cc1
Product: COCCN1C(=O)C(Nc2ccc(C3CCCCC3)cc2)=C(c2ccccc2)S1(=O)=O

Procedure:
The title compound was prepared from 4-chloro-2-(2-methoxyethyl)-5-phenylisothiazol-3(2H)-one 1,1-dioxide and 4-cyclohexylaniline in a similar manner as described for e.g. Examples 9 and 13. 1H NMR (400 MHz, CD3CN): δ 1.19-1.44 (m, 5H), 1.64-1.84 (m, 5H), 2.31-2.40 (m, 1H), 3.38 (s, 3H), 3.72 (t, 2H), 3.90 (t, 2H), 6.67-6.72 (m, 2H), 6.80-6.85 (m, 2H), 7.05-7.14 (m, 4H), 7.19-7.24 (m, 1H), 7.75 (bs, 1H); Mass Spectrum: M+H+ 441.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([NH2:14])[N:3]=1.[Br:15]Br>C(O)(=O)C>[Br:15][C:7]1[C:2]([Cl:1])=[N:3][C:4]([NH2:14])=[N:5][C:6]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: BrBr
Reactant: Nc1nc(Cl)cc(-c2ccccc2)n1
Solvent: CC(=O)O
Product: Nc1nc(Cl)c(Br)c(-c2ccccc2)n1

Procedure:
To 1.5 g (7.3 mM) of 4-chloro-6-phenyl-2-pyrimidinamine is added 75 ml of glacial acetic acid. This mixture is stirred to dissolve and 0.44 ml of bromine is added. The reaction is stirred at ambient temperature for 24 hours. The solution is evaporated to dryness under vacuum to yield 1.75 g of 5-bromo-4-chloro-6-phenyl-2-pyrimidinamine.
Reaction SMILES: [CH2:1]([N:4]1[C:9](=[O:10])[CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH3:14])[N:6]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]3[NH:32][N:31]=[N:30][N:29]=3)=[CH:18][CH:17]=2)[C:5]1=[O:33])[CH2:2][CH3:3].[C:34]([O:40][CH2:41]I)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36].C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:34]([O:40][CH2:41][N:29]1[C:28]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:6]3[C:7]([O:11][CH2:12][CH2:13][CH3:14])=[CH:8][C:9](=[O:10])[N:4]([CH2:1][CH2:2][CH3:3])[C:5]3=[O:33])=[CH:17][CH:18]=2)=[N:32][N:31]=[N:30]1)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]
Reactant: CCCOc1cc(=O)n(CCC)c(=O)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Reactant: CC(C)(C)C(=O)OCI
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCOc1cc(=O)n(CCC)c(=O)n1Cc1ccc(-c2ccccc2-c2nnnn2COC(=O)C(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 79.6 %

Procedure:
A mixture of 3-propyl-6-propyloxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]pyrimidine-2,4(1H,3H)-dione (0.1 g), pivaloyloxymethyl iodide (90 mg) and sodium bicarbonate (35 mg) in DMF (2 ml) was stirred at room temperature for 20 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in chloroform-water. The chloroform layer was dried and evaporated in vacuo to give a syrup. The syrup was column-chromatographed on silica gel to give a colorless syrup (0.1 g, 81%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[C:8](=[C:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:32])[CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)[CH2:20][CH2:19]3)[C:9]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:10]=3[CH2:11][CH2:12][C:3]=12.[H-].[Na+].[CH2:35]([SH:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C=O)C>[Cl:17][C:14]1[CH:15]=[CH:16][C:9]2[C:8](=[C:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:32])[CH2:25][C:26]4[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=4)[CH2:20][CH2:19]3)[C:4]3=[N:5][CH:6]=[CH:7][C:2]([S:42][CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[C:3]3[CH2:12][CH2:11][C:10]=2[CH:13]=1
Reactant: O=C(Cc1cccnc1)N1CCC(=C2c3ccc(Cl)cc3CCc3c(Cl)ccnc32)CC1
Reactant: SCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(Cc1cccnc1)N1CCC(=C2c3ccc(Cl)cc3CCc3c(SCc4ccccc4)ccnc32)CC1
Yield: 8 %

Procedure:
A mixture of the title compound from Example 250 (0.25 grams), sodium hydride (0.11 grams, 60% in mineral oil), benzyl mercaptan (0.13 mL) and anhydrous DMF (15 mL) was stirred while being irradiated with a 200 W lamp for 10 days. Isolation and purification as in Example 257 provided the title compound (0.02 grams, 8%, MH+ 552).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][CH:6]3[CH2:11][CH2:12][N:13]([CH2:15][CH2:16][CH2:17][C:18](=[O:26])[C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[CH2:14][CH:5]3[C:4]=2[CH:3]=1.[CH:27](O)=O.C=O.[OH-].[Na+]>O>[CH3:27][N:7]1[C:8]2[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=2[CH:5]2[CH2:14][N:13]([CH2:15][CH2:16][CH2:17][C:18](=[O:26])[C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH2:12][CH2:11][CH:6]12
Reactant: Cc1ccc2c(c1)C1CN(CCCC(=O)c3ccc(F)cc3)CCC1N2
Reactant: O=CO
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cc1ccc2c(c1)C1CN(CCCC(=O)c3ccc(F)cc3)CCC1N2C

Procedure:
A mixture of 8-methyl-2-[γ-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (7.5 g), formic acid (2.7 g) and formalin (2.2 g) is refluxed for 3 hours. After cooling, to the reaction mixture is added water, and the mixture is made alkaline with aqueous sodium hydroxide and extracted with benzene. The benzene layer is dried over anhydrous sodium sulfate and concentrated. The resulting residue is treated with ethanolic hydrogen chloride in the same manner as described in Example 1 (1) to give the dihydrochloride of the titled compound (4.1 g), m.p. 140° - 145°C (recrystallized from aqueous ethanol).
Reaction SMILES: CN(C)C.CN(C=O)C.Cl/[CH:11]=[C:12]1/[C:13](=[N:22]/[C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)/[S:14][CH:15]2[CH:20]([CH2:21]/1)[CH2:19][CH2:18][CH:17]=[CH:16]2.[C:30]1([SH:36])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O>[Cl:29][C:26]1[CH:27]=[CH:28][C:23](/[N:22]=[C:13]2\[S:14][CH:15]3[CH:20]([CH2:21]\[C:12]\2=[CH:11]/[S:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:19][CH2:18][CH:17]=[CH:16]3)=[CH:24][CH:25]=1
Reactant: Cl/C=C1\CC2CCC=CC2S\C1=N/c1ccc(Cl)cc1
Reactant: Sc1ccccc1
Agent: CN(C)C
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccc(/N=C2\SC3C=CCCC3C\C2=C/Sc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
65 mg of trimethylamine and 1 ml of DMF solution including {3-[1-chloro-(E)-methylidene]-3,4,4a,5,6,8a-hexahydro-thiochromene-(2Z)-ylidene}-(4-chloro-phenyl)-amine were added to 2 ml of DMF solution including 47 mg of thiophenol at 0° C. The resulting solution was stirred at room temperature for an additional 30 minutes, and added with water, and then extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.17 g of the title compound.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2=[C:9]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:10][N:11]=[C:5]2[N:4]2[C@H:19]3[CH2:24][CH2:23][CH2:22][C@H:20]3[N:21]=[C:3]12.I[CH2:26][CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:10][N:11]([CH2:26][CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[C:5]=2[N:4]2[C@H:19]3[CH2:24][CH2:23][CH2:22][C@H:20]3[N:21]=[C:3]12
Reactant: ICC1CCOCC1
Reactant: CN1C(=O)c2c(n[nH]c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CN1C(=O)c2c(Nc3ccccc3)nn(CC3CCOCC3)c2N2C1=N[C@@H]1CCC[C@@H]12
Temperature: 140 °C

Procedure:
A mixture of (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-one (50 mg, 0.155 mmol), 4-(iodomethyl)-tetrahydro-2H-pyran (70 mg, 0.310 mmol), and Cs2CO3 (101 mg, 0.310 mmol) in DMF (1 mL) is heated in microwave at 140° C. for 30 min. After cooling, the mixture is filtered through a 0.45 μm microfilter, and the filtrate is purified by a semi-preparative HPLC to give pure product as white powder. MS (ESI) m/z 421.2 [M+H]+.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:11]=2[C:12]([O:14]C)=[O:13])[CH2:3]1.[CH3:21][C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:23]=1[C:29]1[O:30][C:31]([CH3:36])=[C:32]([CH2:34]I)[N:33]=1>>[CH3:21][C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:23]=1[C:29]1[O:30][C:31]([CH3:36])=[C:32]([CH2:34][O:1][CH:2]2[CH2:7][CH2:6][CH2:5][CH:4]([O:8][CH2:9][C:10]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:11]=3[C:12]([OH:14])=[O:13])[CH2:3]2)[N:33]=1
Reactant: Cc1ccc(-c2nc(CI)c(C)o2)c(C)c1
Reactant: COC(=O)c1c(C)cccc1COC1CCCC(O)C1
Product: Cc1ccc(-c2nc(COC3CCCC(OCc4cccc(C)c4C(=O)O)C3)c(C)o2)c(C)c1

Procedure:
Using methyl 2-(3-hydroxycyclohexyloxymethyl)-6-methylbenzoate and 2-(2,4-dimethylphenyl)-4-iodomethyl-5-methyloxazole as starting materials in the procedure of Example XXXI, gave the product 62 of molecular weight 463.58 (C28H33NO5), MS(ESI): 464.22 (M+H+).
Reaction SMILES: [C@H:1]([NH:5][C:6]1[C:7](OS(C(F)(F)F)(=O)=O)=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2].[F:28][C:29]1[CH:30]=[CH:31][C:32]2[O:36][C:35](B(O)O)=[CH:34][C:33]=2[CH:40]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[C@H:1]([NH:5][C:6]1[C:7]([C:35]2[O:36][C:32]3[CH:31]=[CH:30][C:29]([F:28])=[CH:40][C:33]=3[CH:34]=2)=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][CH:10]=2)([CH2:3][CH3:4])[CH3:2]
Reactant: OB(O)c1cc2cc(F)ccc2o1
Reactant: CC[C@@H](C)Nc1nc2cc(C(=O)OC)ccc2nc1OS(=O)(=O)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CC[C@@H](C)Nc1nc2cc(C(=O)OC)ccc2nc1-c1cc2cc(F)ccc2o1
Temperature: 90 °C
Reaction time: 1 h

Procedure:
To a solution of (R)-methyl 3-(sec-butylamino)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate (400 mg, crude) in dioxane (5 mL) was added 5-fluorobenzofuran-2-ylboronic acid (441 mg, 2.45 mmol), K3PO4 (620 mg, 2.94 mmol), and Pd(PPh3)4 (57 mg, 0.05 mmol). The resulting solution was stirred for 1 h at 90° C. and then quenched by the addition of dichloromethane (200 mL) and washed with water (3×50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (5% ethyl acetate in petroleum ether) to afford (R)-methyl 3-(sec-butylamino)-2-(5-fluorobenzofuran-2-yl)quinoxaline-6-carboxylate as a yellow solid (100 mg, 24% 2 steps).
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][C@@H:8]([CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)[CH2:9][O:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15]([CH:17]=[CH:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](F)[CH:20]=2)[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:37][O-:38].[Na+]>CO>[C:1]([O:5][C:6](=[O:36])[NH:7][C@@H:8]([CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)[CH2:9][O:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15]([CH:17]=[CH:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([O:38][CH3:37])[CH:20]=2)[CH:16]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H](COc1cncc(C=Cc2ccnc(F)c2)c1)Cc1c[nH]c2ccccc12
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(C=Cc2cncc(OC[C@H](Cc3c[nH]c4ccccc34)NC(=O)OC(C)(C)C)c2)ccn1

Procedure:
A mixture of Example 216B (100 mg, 0.2 mmol), NaOMe (25% in MeOH) (1 mL) in MeOH (10 mL) was refluxed for 8 hrs. The mixture was concentrated to give the crude product.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]([OH:13])=O)=[CH:8][C:9]=1[CH3:10])=[O:4].[NH2:14][CH:15]([C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1)[CH3:16].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11](=[O:13])[NH:14][CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)[CH3:16])=[CH:8][C:9]=1[CH3:10])=[O:4]
Reactant: COC(=O)c1sc(C(=O)O)cc1C
Reactant: CC(N)c1cccc(O)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)c1sc(C(=O)NC(C)c2cccc(O)c2)cc1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75.8 %

Procedure:
To a solution of 3-methyl-thiophene-2,5-dicarboxylic acid 2-methyl ester (0.1 g, 0.5 mmol) and 3-(1-amino-ethyl)-phenol (82 mg, 0.6 mmol) in DMF (4 ml) was added at rt triethylamine (0.1 ml, 0.75 mmol), HOBT (81 mg, 0.6 mmol) and HBTU (228 mg, 0.6 mmol). The mixture was stirred at rt for 30 min, then quenched with 1NHCl and extracted with EtOAc. The layers were separated. The organic layer was washed with brine, then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 30-70% EtOAc in hexane to afford the desired product (121 mg, 75% yield).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=2[F:24])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1>[F:24][C:15]1[CH:16]=[C:17]([C:20]([F:21])([F:22])[F:23])[CH:18]=[CH:19][C:14]=1[N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2F)CC1
Agent: Cl
Solvent: C1COCCO1
Product: Fc1cc(C(F)(F)F)ccc1N1CCNCC1
Yield: 94 %

Procedure:
A mixture of 3.11 g (9 mmol) 4-(2-Fluoro-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester in 20 ml dioxane was treated with 8.93 ml 4N HCl in dioxane for 2 h at 80° C. The mixture was concentrated and treated with 20 ml water, 20 ml 2M Na2CO3 and extracted with 50 ml EtOAc. The organic phase was washed with 30 ml saturated NaCl. All aqueous phases were combined and extracted with 50 ml EtOAc. The combined organic phases were dried with MgSO4 and evaporated to yield 2.1 g (95%) of the title compound as brownish crystals.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:28])[N:5]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:6]([C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[N:7]2.[CH3:29][N:30]1C(=O)CCC1>[C-]#N.[Zn+2].[C-]#N>[C:29]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:28])[N:5]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:6]([C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[N:7]2)#[N:30]
Reactant: CN1CCCC1=O
Reactant: C[C@H](NC(=O)OC(C)(C)C)c1nc2cccc(Br)c2c(=O)n1-c1ccccc1
Agent: [C-]#N
Agent: [Zn+2]
Product: C[C@H](NC(=O)OC(C)(C)C)c1nc2cccc(C#N)c2c(=O)n1-c1ccccc1
Temperature: 90 °C

Procedure:
(S)-tert-butyl (1-(5-bromo-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)carbamate (500 mg, 1.13 mmol), zinc cyanide (166 mg, 1.41 mmol), and tetrakis(triphenylphosphine)Pd(0) (124 mg, 0.11 mmol) were combined in NMP (5 mL). The mixture was degassed under Ar and heated to 90° C. overnight. The reaction was poured into EtOAc, washed with water (3×), and purified by flash chromatography (40 g silica, 0-50% EtOAc/hexanes) to give (S)-tert-butyl (1-(5-cyano-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)carbamate as a white solid. ES/MS 391.2 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=O)=[C:17]([O:25][CH3:26])[CH:16]=2)[N:10]=1.[F:27][C:28]1[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][C:29]=1[NH2:30].C[Al](C)C>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:13][C:12](=[O:14])[N:11]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([NH:30][C:29]3[CH:31]=[CH:32][C:33]([CH3:35])=[CH:34][C:28]=3[F:27])=[O:21])=[C:17]([O:25][CH3:26])[CH:16]=2)[N:10]=1
Reactant: Cc1ccc(N)c(F)c1
Reactant: COC(=O)c1ccc(-n2nc(-c3c(F)cccc3Cl)[nH]c2=O)cc1OC
Agent: C[Al](C)C
Product: COc1cc(-n2nc(-c3c(F)cccc3Cl)[nH]c2=O)ccc1C(=O)Nc1ccc(C)cc1F
Yield: 38.4 %

Procedure:
The title compound was prepared according to the procedure described in Example-31, by using methyl 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (step-2 of Intermediate-15, 0.100 g, 0.26 mmol), 2-fluoro-4-methyl aniline (0.050 g, 0.39 mmol) and trimethyl aluminium (2M solution in toluene) (0.5 mL) to afford 0.047 g of desired product. 1HNMR (DMSO-d6): δ 2.30 (s, 3H), 4.03 (s, 3H), 7.02 (d, J=8.1 Hz, 1H), 7.14 (d, J=11.7 Hz, 1H), 7.51 (t, 1H), 7.58 (d, 1H), 7.65-7.75 (m, 2H), 7.85 (s, 1H), 8.04-8.10 (m, 2H), 10.07 (br s, 1H), 12.65 (br s, 1H); MS (m/z): 469.16 [M−H]−.
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: CCCCCCCCCCC(CO)CCCCCCCC
Reactant: CC(C)=O
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: Cl[C:2]([O:4][CH3:5])=[O:3].[NH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:21]([N:23]([CH3:25])[CH3:24])=[O:22])=[C:11]([S:13]([NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])=[O:14])[CH:12]=1.C([O-])(O)=O.[Na+]>CC#N.C(OCC)(=O)C>[C:17]([NH:16][S:13]([C:11]1[CH:12]=[C:7]([NH:6][C:2]([O:4][CH3:5])=[O:3])[CH:8]=[CH:9][C:10]=1[C:21]([N:23]([CH3:25])[CH3:24])=[O:22])(=[O:15])=[O:14])([CH3:20])([CH3:19])[CH3:18]
Reactant: COC(=O)Cl
Reactant: CN(C)C(=O)c1ccc(N)cc1S(=O)(=O)NC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COC(=O)Nc1ccc(C(=O)N(C)C)c(S(=O)(=O)NC(C)(C)C)c1
Yield: 83.3 %

Procedure:
0.47 g of methyl chloroformate is added dropwise to a suspension of 1.50 g of 5-amino-N-tert.-butyl-2-dimethylaminocarbonyl-benzenesulfonamide (Example e) and 1.46 g of NaHCO3 in 50 ml of CH3CN at 0° C. When the reaction has ended, the reaction mixture is taken up in ethyl acetate and the mixture is washed with 1N hydrochloric acid, dried over MgSO4 and concentrated. 1.48 g of N-tert.-butyl-2-dimethylaminocarbonyl-5-methoxycarbonylamino-benzenesulfonamide are thus obtained; m.p.: 184-188° C.
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:28][C:29]1[CH:38]=[C:37]2[C:32]([C:33]([N:46]3[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]3)=[N:34][C:35]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[OH:45])=[N:36]2)=[CH:31][CH:30]=1.[OH:52][C@@H:53]([CH2:57][CH:58]([CH3:60])[CH3:59])[C:54](O)=[O:55].C(N(CC)CC)C>CN(C=O)C>[OH:52][C@@H:53]([CH2:57][CH:58]([CH3:60])[CH3:59])[C:54]([N:49]1[CH2:50][CH2:51][N:46]([C:33]2[C:32]3[C:37](=[CH:38][C:29]([CH3:28])=[CH:30][CH:31]=3)[N:36]=[C:35]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[OH:45])[N:34]=2)[CH2:47][CH2:48]1)=[O:55]
Reactant: CC(C)C[C@H](O)C(=O)O
Reactant: Cc1ccc2c(N3CCNCC3)nc(-c3ccccc3O)nc2c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc2c(N3CCN(C(=O)[C@@H](O)CC(C)C)CC3)nc(-c3ccccc3O)nc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Under an N2 atmosphere, BOP (137 mg, 0.31 mmol) was added in a single portion to a stirring solution of 2-(7-methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (100 mg, 0.31 mmol), (S)-2-hydroxy-4-methylpentanoic acid (41 mg, 0.31 mmol), and triethylamine (43 μL, 0.31 mmol) in DMF (0.5 ml). After stirring the mixture for 1 h at room temperature, it was partitioned between H2O and ether. The organic phase was washed with H2O (3×20 mL), dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 1:1 ethyl acetate/hexane gave (S)-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-4-methylpentan-1-one as a white solid. LC/MS: m/z 435.3 (M+H)+ at 2.62 min (10-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.44 (dd, J=8.2, 1.7 Hz, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.67 (s, 1H), 7.40-7.36 (m, 2H), 6.96-6.93 (m, 2H), 4.92 (d, J=7.2 Hz, 1H) 4.41-4.36 (m, 1H), 4.06-3.67 (m, 8H), 2.51 (s, 3H), 1.85-1.73 (m, 1H), 1.49-1.35 (m, 2H), 0.93-0.91 (m, 6H).