Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)(C(F)(F)F)=O.[F:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([F:19])[C:10]=1[C:20]1[N:25]=[C:24]2[NH:26][N:27]=[C:28](I)[C:23]2=[CH:22][N:21]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1>>[F:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([F:19])[C:10]=1[C:20]1[N:25]=[C:24]2[NH:26][N:27]=[C:28]([C:34]3[CH:33]=[N:32][N:31]([CH3:30])[CH:35]=3)[C:23]2=[CH:22][N:21]=1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: COc1cc(OC)c(F)c(-c2ncc3c(I)n[nH]c3n2)c1F
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(OC)c(F)c(-c2ncc3c(-c4cnn(C)c4)n[nH]c3n2)c1F

Procedure:
This compound was prepared as a TFA salt by using procedures analogous to those described for the synthesis of Example 7, Step 3 starting from 6-(2,6-difluoro-3,5-dimethoxyphenyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidine and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. LCMS (M+H)+=373.0. 1H NMR (300 MHz, DMSO-d6) δ: 14.11 (s, 1H), 9.74 (s, 1H), 8.56 (s, 1H), 8.17 (s, 1H), 7.17 (t, J=8.1 Hz, 1H), 3.95 (s, 3H), 3.93 (s, 3H).
Reaction SMILES: C([O:3][C:4](=[O:33])[C:5]([CH3:32])([O:7][C:8]1[CH:13]=[CH:12][C:11]([C@@H:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C@@H:20]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)[CH3:21])[CH2:15]2)=[CH:10][CH:9]=1)[CH3:6])C.[OH-].[K+].[ClH:36]>C(O)C.O1CCCC1.C(OCC)(=O)C>[ClH:36].[CH3:6][C:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([C@@H:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C@@H:20]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)[CH3:21])[CH2:15]2)=[CH:10][CH:9]=1)([CH3:32])[C:4]([OH:33])=[O:3]
Reactant: CCOC(=O)C(C)(C)Oc1ccc([C@@H]2CC[C@H](N[C@H](C)c3cccc4ccccc34)C2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: CCOC(C)=O
Product: C[C@@H](N[C@H]1CC[C@@H](c2ccc(OC(C)(C)C(=O)O)cc2)C1)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 77 %

Procedure:
2-Methyl-2-{4-[(1R,3S)-3-{[(1R)-1-(naphthalen-1-yl)ethyl]amino}cyclopentyl]phenoxy}propanoic acid ethyl ester (130 mg, 0.29 mmol) was dissolved in ethanol (2 mL) and tetrahydrofuran (2 mL), followed by addition of 2N aqueous potassium hydroxide solution, and the mixture was stirred overnight at room temperature. 1N hydrochloric acid was added dropwise to the reaction mixture to make the reaction solution acidic, and the solvent was distilled off under reduced pressure. The aqueous phase was extracted with ethyl acetate, the extracted solution was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue obtained was dissolved in ethyl acetate (3 mL), followed by addition of an ethyl acetate solution of 1N hydrochloric acid (1 mL), and the solvent was distilled off under reduced pressure. Ethyl acetate and hexane were added to the residue, followed by treatment with ultrasonic waves, and then the solid matter generated was collected by filtration to give the title compound (102 mg, 77%).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:10]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:8]=[CH:7][C:6]=2[C@@H:5]2[CH2:16][N:17](C(OC(C)(C)C)=O)[CH2:18][C@H:4]2[NH:3]1.[ClH:26]>O1CCOCC1>[ClH:26].[F:15][C:12]([F:13])([F:14])[C:10]1[C:11]2[C:2](=[O:1])[NH:3][C@@H:4]3[CH2:18][NH:17][CH2:16][CH:5]3[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)(C)OC(=O)N1C[C@H]2NC(=O)c3c(cccc3C(F)(F)F)[C@@H]2C1
Agent: Cl
Solvent: C1COCCO1
Product: O=C1N[C@@H]2CNCC2c2cccc(C(F)(F)F)c21
Temperature: 25 °C
Reaction time: 1 h
Yield: 91 %

Procedure:
To a solution of the second eluting peak from Example 13, Part A, (3 as,9bR)-tert-butyl 5-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]isoquinoline-2(9bH)-carboxylate (100 mg, 0.28 mmol) in 4 mL of dioxane was added 1 mL of 12 N HCl. The resulting solution was stirred at ambient temperature for 1 h and then was concentrated. The residue was azeotroped with toluene and dried in vacuo to afford a foam. This foam was triturated 3× with ether and dried in vacuo to afford 75 mg (91%) of the title compound of Example 14 as an off-white powder. 1H NMR (DMSO-D6): δ 9.8 (broad s, 1H), 9.6 (broad s, 1H), 9.00 (s, 1H), 7.83 (d, 1H, J=8.2 Hz), 7.73 (t, 1H, J=7.7 Hz), 7.58 (d, 1H, J=7.7 Hz), 3.94-3.90 (m, 1H), 3.67-3.60 (m, 1H), 3.55-3.50 (m, 1H), 3.37-3.32 (m, 1H), 3.20-3.10 (m, 2H). LRMS (ESI): 257.16 (M+H)+.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=2[O:2]1.[Cl:15][C:16]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:17]=1[C:18](O)=[O:19].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C(Cl)CCl>[Cl:15][C:16]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:17]=1[C:18]([C:6]1[CH:7]=[C:8]2[O:9][CH2:1][O:2][C:3]2=[CH:4][C:5]=1[CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:19]
Reactant: COC(=O)Cc1ccc2c(c1)OCO2
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1Cl
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: ClCCCl
Product: COC(=O)Cc1cc2c(cc1C(=O)c1ccc([N+](=O)[O-])cc1Cl)OCO2

Procedure:
The title compound was prepared from methyl 3,4-methylenedioxyphenylacetate (12.5 g, 64.4 mmol) in ClCH2CH2Cl (150 mL), 2-chloro-4-nitrobenzoic acid (25.0 g, 124 mmol) and P2O5 (37 g) as a yellow solid (11 g, 29 mmol, 45%). 1H NMR (CDCl3) 8.15 (s, 1H), 8.14 (d, J=8.4, 1H), 7.58 (d, J=8.4, 1H), 6.84 (s, 1H), 6.71 (s, 1H), 6.05 (s, 2H), 4.03 (s, 2H), 3.73 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Br:12]Br.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>O.CO>[Br:12][C:9]1[CH:10]=[CH:11][C:2]([CH3:1])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: BrBr
Reactant: COC(=O)c1ccccc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: Cc1ccccc1
Solvent: O
Product: COC(=O)c1cc(Br)ccc1C
Yield: 17.2 %

Procedure:
To 50 g of Na-X type zeolite dry powder (Zeolum type F-9; 100 meshes or finer, produced by Tosoh Corporation) was added dropwise 7.51 g (50.0 mmol) of methyl 2-methylbenzoate with stirring. Further, 3.9 ml (75 mmol) of bromine was added dropwise thereto at 45˜50° C., and the mixture was stirred at 80° C. for 1 hour. To the reaction mixture was added a solution of potassium carbonate (5.5 g) in water (50 ml) and methanol (250 ml). The mixture was stirred at room temperature for 10 minutes and filtered. The residual zeolite powder was washed with warmed hydrous methanol (10%, 250 ml). The filtrate and the washing were combined and concentrated. The residue was diluted with ethyl acetate, washed twice with water, dried and concentrated. The residue (2.98 g) was subjected to silica gel column chromatography (eluted with n-hexane:toluene=10:1 and then 5:1 and then 3:1) to obtain 1.97 g (8.60 mmol) of methyl 5-bromo-2-methylbenzoate as crystals.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:24][CH2:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:27]=1[C:28](=[O:44])[N:29]([CH:36]1[CH2:41][CH2:40][C:39](=[O:42])[NH:38][C:37]1=[O:43])[C:30]2=[O:35].C(N(CC)CC)C>CN(C=O)C>[O:43]=[C:37]1[CH:36]([N:29]2[C:28](=[O:44])[C:27]3[C:31](=[CH:32][CH:33]=[CH:34][C:26]=3[CH2:25][NH:24][C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)=[O:10])[C:30]2=[O:35])[CH2:41][CH2:40][C:39](=[O:42])[NH:38]1
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reactant: Cc1cccc(C(=O)O)n1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1cccc(C(=O)NCc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 41.8 %

Procedure:
A mixture of 6-methylpicolinic acid (0.27 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (25 mL) was stirred at ambient temperature under nitrogen for 1 hour. 4-Aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) were added, and the mixture was allowed to stir for 16 hours. The solvent was evaporated under vacuum, and the residue was purified by preparative HPLC, eluting with 45:55 acetonitrile-water, providing 0.34 g of the product in 54% yield: mp 197-199° C.; 1H NMR (DMSO-d6) δ 2.06-2.11 (m, 1H), 2.53-2.65 (m, 2H), 2.58 (s, 3H), 2.84-2.94 (m, 1H), 4.96 (d, J=6.3 Hz, 2H), 5.18 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.49 (dd, J=6.8 Hz, J=1.9 Hz, 1H), 7.69 (dd, J=8.5 Hz, J=4.1 Hz, 1H), 7.79-7.93 (m, 4H), 9.36 (t, J=6.3 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 23.9, 30.9, 38.3, 48.9, 119.2, 121.9, 126.3, 127.2, 131.6, 133.0, 134.8, 137.9, 139.2, 149.0, 157.3, 164.5, 167.0, 167.6, 169.8, 172.8; Anal. calcd for C21H18N4O5.0.6H2O: C, 60.45; H, 4.63; N, 13.42. Found: C, 60.47; H, 4.53; N, 13.36.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:33]=[CH:34][CH:35]=1)[C:6]([C:8]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][N:11]=[C:10]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[N:9]=1)=[O:7])=O.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.[BH3-]C#N.[Na+]>O1CCOCC1>[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([CH2:1][C:3]2[CH:4]=[C:5]([CH:33]=[CH:34][CH:35]=2)[C:6]([C:8]2[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][N:11]=[C:10]([NH:19][C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]4)=[CH:24][CH:25]=3)[N:9]=2)=[O:7])[CH2:39][CH2:38]1
Reactant: CN1CCNCC1
Reactant: CCOC(=O)c1cnc(Nc2ccc(N3CCN(C)CC3)cc2)nc1C(=O)c1cccc(C=O)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: C1COCCO1
Product: CCOC(=O)c1cnc(Nc2ccc(N3CCN(C)CC3)cc2)nc1C(=O)c1cccc(CN2CCN(C)CC2)c1
Temperature: 70 °C
Reaction time: 48 h

Procedure:
A solution of Example 215C (100 mg, 0.2 mmol) in dioxane (5 mL) was added 1-methylpiperazine (40 mg, 0.4 mmol) and NaCNBH3 (25 mg, 0.5 mmol). The reaction mixture was stirred at 70° C. for 2 days, and concentrated. The residue was purified by flash chromatography, eluted with 0-20% gradient methanol in methylene chloride to yield the title compound. MS (DCI/NH3) m/z 557 (M+H).
Reaction SMILES: CN(CC[C:12]1[NH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([C:21]([NH2:23])=[O:22])=[CH:16][CH:15]=2)CC1C=CC=CC=1>C(O)C>[CH2:21]([OH:22])[CH3:17].[CH3:14][NH:13][CH2:12][CH2:20][C:20]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21]([NH2:23])=[O:22])[CH:18]=2)[NH:13][CH:12]=1
Reactant: CN(CCc1cc2cc(C(N)=O)ccc2[nH]1)Cc1ccccc1
Solvent: CCO
Product: CNCCc1c[nH]c2ccc(C(N)=O)cc12
Yield: 155.6 %

Procedure:
A solution of 3-[2-[(methyl(phenylmethyl)amino]ethyl]-1H-indole-5-carboxamide (1.05 g) in absolute ethanol (200 ml) was hydrogenated over pre-reduced palladium oxide on charcoal (10%, 0.5 g) for 2.5 hours at room temperature and pressure. The catalyst was filtered off and the filtrate evaporated in vacuo to give the title compound (0.7 g) as a colourless crystalline solid. T.L.C. Silica, ethanol:water (1:1) Rf 0.3
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:12]([O-:14])=[O:13])=[C:7]([CH:11]=1)[C:8](O)=[O:9].C[N:16](C=O)C.C(Cl)(=O)C(Cl)=O.N>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:12]([O-:14])=[O:13])=[C:7]([CH:11]=1)[C:8]([NH2:16])=[O:9]
Reactant: CN(C)C=O
Reactant: COc1ccc([N+](=O)[O-])c(C(=O)O)c1
Agent: N
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Product: COc1ccc([N+](=O)[O-])c(C(N)=O)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 56 %

Procedure:
To a solution of 5-methoxy-2-nitrobenzoic acid (18.0 g, 91.3 mmol) and DMF (0.1 mL) in THF (150 mL) was added dropwise oxalyl chloride (12.7 g, 100 mmol) under ice-cooling, and the mixture was stirred at 0° C. for 1 hr, and then at room temperature for 3 hr. This solution was added dropwise to aqueous ammonia (7% aqueous solution, 200 mL) under ice-cooling. The reaction solution was concentrated under reduced pressure to evaporated THF, and the precipitated insoluble material was collected by filtration. The filtered cake was washed with water to give 5-methoxy-2-nitrobenzamide as a pale-yellow powder (10.0 g, 56%).
Reaction SMILES: C1(C2C=CC([CH:8]=[O:9])=CC=2)CC1.Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:23])([CH3:22])[CH2:20][CH3:21])=[CH:15][CH:14]=1.[Li]CCCC.CN(C=O)C>>[CH3:22][C:19]([C:16]1[CH:17]=[CH:18][C:13]([CH:8]=[O:9])=[CH:14][CH:15]=1)([CH3:23])[CH2:20][CH3:21]
Reactant: CCC(C)(C)c1ccc(Br)cc1
Reactant: O=Cc1ccc(C2CC2)cc1
Agent: [Li]CCCC
Solvent: CN(C)C=O
Product: CCC(C)(C)c1ccc(C=O)cc1
Yield: 90 %

Procedure:
The title compound was synthesized in analogy to 4-cyclopropyl benzaldehyde (described in example S53) using 1-bromo-4-(1,1-dimethylpropyl)-benzene [synthesized in analogy to a procedure described in J. Chem. Res. Miniprint. 12:2701-2733 (1997)] (250 mg, 1.10 mmol), n-BuLi (825 μl, 1.6M solution in hexane, 1.32 mmol) and DMF (427 μl, 5.50 mmol). The isolated residue was purified by flash column chromatography (1:9 ether:pentane) to give 4-(1,1-dimethylpropyl)-benzaldehyde (175 mg, 90%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 9.99 (s, 1H), 7.82 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 2H), 1.69 (q, J=7.5 Hz, 2H), 1.32 (s, 6H), 0.68 (t, J=7.5 Hz, 3H).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5](=[O:18])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:7]=1[CH:15]([CH3:17])[CH3:16].C(N(CC)CC)C.[CH:26]([C:29]1[NH:30][CH:31]=[CH:32][N:33]=1)([CH3:28])[CH3:27]>CN(C=O)C.O>[CH:26]([C:29]1[N:30]([CH2:2][CH2:3][O:4][C:5](=[O:18])[C:6]2[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][C:7]=2[CH:15]([CH3:17])[CH3:16])[CH:31]=[CH:32][N:33]=1)([CH3:28])[CH3:27]
Reactant: CC(C)c1cc([N+](=O)[O-])ccc1C(=O)OCCBr
Reactant: CC(C)c1ncc[nH]1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)c1cc([N+](=O)[O-])ccc1C(=O)OCCn1ccnc1C(C)C
Yield: 43.4 %

Procedure:
2-Isopropyl-4-nitro-benzoic acid 2-bromo-ethyl ester (0.19 g, 0.6 mmol) was dissolved in DMF (5 mL), then triethylamine (0.5 mL, 3.6 mmol) and 2-isopropylimidazole (0.2 g, 1.8 mmol) were added. The mixture was heated at reflux for 15 h then allowed to cool, diluted with water and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography on silica gel (60-120 mesh), eluting with ethyl acetate, to afford 2-isopropyl-4-nitro-benzoic acid 2-(2-isopropyl-imidazol-1-yl)-ethyl ester (90 mg, 43%) as an oil.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[N:5][N:4]=[C:3]1[NH2:8].[N:9]([C:12](OC1C=CC=CC=1)=[O:13])=[C:10]=[O:11]>C(#N)C>[CH3:7][C:6]1[N:2]([CH3:1])[C:3]2=[N:8][C:10](=[O:11])[NH:9][C:12](=[O:13])[N:4]2[N:5]=1
Reactant: O=C=NC(=O)Oc1ccccc1
Reactant: Cc1nnc(N)n1C
Solvent: CC#N
Product: Cc1nn2c(=O)[nH]c(=O)nc2n1C
Yield: 138.2 %

Procedure:
After suspending 4,5-dimethyl-4H-[1,2,4]triazol-3-ylamine (CAS 53132-83-5) (7.6 g) in acetonitrile (80 ml), a solution of phenyl isocyanatoformate (5.2 g) in acetonitrile (40 ml) was slowly added dropwise while heating to reflux. After heating to reflux for 6 hours, the reaction mixture was cooled on ice. The insoluble matter was collected by filtration to obtain the title compound (7.98 g).
Reaction SMILES: [CH2:1]([N:3]([CH2:12][CH3:13])[C:4](=[O:11])[C:5]([CH3:10])([CH3:9])[C:6](O)=[O:7])[CH3:2].C(Cl)(=O)C([Cl:17])=O>C1C=CC=CC=1.CN(C)C=O>[CH2:1]([N:3]([CH2:12][CH3:13])[C:4](=[O:11])[C:5]([CH3:10])([CH3:9])[C:6]([Cl:17])=[O:7])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCN(CC)C(=O)C(C)(C)C(=O)O
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CCN(CC)C(=O)C(C)(C)C(=O)Cl
Reaction time: 1 h

Procedure:
To a stirred suspension of the compound (1d) (6.6 g, 35.2 mmol) in benzene (25 ml) and freshly distilled oxalyl chloride (5.6 g, 44 mmol) was added at ambient temperature dimethylformamide (2 drops). After 1 hour at ambient temperature, additional dimethylformamide (2 drops) was added and the reaction mixture stirred for additional hour. The solvent was removed in vacuo to give a yellow liquid. The liquid was distilled at reduced pressure to give the desired product as a colorless liquid bp 74°-75° C. at 0.3 mmHg.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:17]([N+:24]([O-])=O)=[CH:16][C:15]=1[N+:27]([O-])=O)[C:9](=[O:13])[O:10][CH2:11][CH3:12]>C(OCC)(=O)C.[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([C:14]1[C:19]([C:20]([F:21])([F:23])[F:22])=[CH:18][C:17]([NH2:24])=[CH:16][C:15]=1[NH2:27])[C:9](=[O:13])[O:10][CH2:11][CH3:12]
Reactant: CCOC(=O)N(c1ccccc1Cl)c1c([N+](=O)[O-])cc([N+](=O)[O-])cc1C(F)(F)F
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)N(c1ccccc1Cl)c1c(N)cc(N)cc1C(F)(F)F
Reaction time: 11 h
Yield: 97.7 %

Procedure:
Ethyl 2-chlorophenyl[2,4-dinitro-6-(trifluoromethyl)phenyl]carbamate (0.645 g) was dissolved in ethyl acetate (100 ml), and to the solution was added 10% Pd—C (0.58 g). The reaction mixture was stirred under hydrogen atmosphere for 11 hours. The catalyst was filtered, and washed with ethyl acetate. The filtrate and washing were combined and concentrated in vacuo to give the title compound (0.543 g, 98%).
Reaction SMILES: [CH2:1]([Li])CCC.[CH3:6]/[C:7](=[CH:10]\[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)/[CH2:8][OH:9].BrCBr.C([Mg]Cl)(C)(C)C.[Cl-].[NH4+]>C(OCC)C>[CH3:6][C:7]1([CH2:8][OH:9])[CH2:1][CH:10]1[C:11]1[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=1
Reactant: [Li]CCCC
Reactant: C/C(=C\c1ccc(C)cc1)CO
Agent: CC(C)(C)[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: BrCBr
Product: Cc1ccc(C2CC2(C)CO)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 90 %

Procedure:
n-Butyllithium (1.6 molar in hexanes; 33.2 ml; 53 1 mmol) was added dropwise to (2E)-2-methyl-3-(4-methylphenyl)-2-propen-1-ol (8.61 g, 53 1 mmol) in dry diethyl ether (120 ml) at 0° C. under nitrogen. After 10 minutes, dibromomethane (46.6 g; 265 mmol) was added dropwise, followed, after 15 minutes, by t-butyl magnesium chloride (2 molar in diethyl ether; 133 ml; 265 mmol). The reaction was then slowly warmed up to room temperature and stirred overnight. It was then cooled into an ice-water bath and a saturated aqueous ammonium chloride solution (300 ml) was added (initially dropwise, exothermic). After warming to room temperature, diethyl ether (200 ml) was added and the mixture shaken vigorously. The organic phase was washed with water (600 ml) and brine (300 ml). Each aqueous phase was re-extracted with diethyl ether (300 ml). Combined extracts were dried over solid anhydrous sodium sulfate. The product was purified by column chromatography on silica gel (heptane/ethyl acetate 5:1 to 2:1) followed by bulb-to-bulb distillation (120° C./1 mbar). 2.21 g of 90% pure material was obtained as a colorless liquid (11.3 mmol; 21%).
Reaction SMILES: O1CCOCC1.[CH:7]1([CH:10](O)[C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)[CH2:9][CH2:8]1.[BrH:20]>O>[CH3:18][S:17][C:14]1[CH:15]=[CH:16][C:11](/[CH:10]=[CH:7]/[CH2:8][CH2:9][Br:20])=[CH:12][CH:13]=1
Reactant: Br
Reactant: CSc1ccc(C(O)C2CC2)cc1
Solvent: C1COCCO1
Solvent: O
Product: CSc1ccc(/C=C/CCBr)cc1
Reaction time: 0.5 h

Procedure:
To 10 ml of dioxane solution containing 5 g of 1-(cyclopropyl, hydroxymethyl)-4-methylthiobenzene was added dropwise 6 ml of 47% of hydrobromic acid under an ice-cooled condition, then the mixture was stirred for 30 minutes, and the reaction mixture was concentrated under a reduced pressure. To the residue thus obtained was added water, then extracted with ether, the extract was washed with water and dried with anhydrous sodium sulfate, and concentrated to dryness. The residue was recrystallized from methanol to yield 2.2 g of 4-(4'-methylthiophenyl)-3(E)-butenylbromide in the form of colorless flake-like crystals. Melting point: 54°-56° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:20][OH:21])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH:20]=[O:21]
Reactant: OCc1ccc(NCCCCCc2ccccc2)c(Br)c1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=Cc1ccc(NCCCCCc2ccccc2)c(Br)c1

Procedure:
A solution of 5-bromopentylbenzene [14469-83-1] (4 g, 17.6 mmol) in HMPA (55 g) was treated with 4-amino-3-bromobenzemethanol [146019-46-7] and dry K2CO3 (4.87 g, 35.2 mmol) for ˜18 h at 120° C. The mixture was cooled to rt, poured onto water (600 mL) and extracted with ethyl acetate (200 mL). The organic phase was washed with water (200 mL), dried over Na2SO4, concentrated, and purified by chromatography (ethyl acetate/hexane) to give (3-bromo-4-((5-phenylpentyl)amino)phenyl)methanol (2.24 g, 37%). A solution of (3-bromo-4-((5-phenylpentyl)amino)phenyl)methanol (8.0 g, 23 mmol) in dichloromethane (160 mL) was treated with silica gel (24 g) and PCC (14.9 g, 69 mmol) at rt for ˜18 h. The mixture was concentrated, and purified by chromatography on silica gel (ethyl acetate-hexane) to give 3-bromo-4-((5-phenylpentyl)amino)benzaldehyde Intermediate-21 (3.5 g, 44%).
Reaction SMILES: CC([O-])(C)C.[K+].[Si:7]([O:14][CH2:15][CH2:16][N:17]1[C:23]2[N:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:21]2[CH:28]=[CH:29][CH:30]=[CH:31][C:20]=2[CH2:19][C:18]1=[O:32])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[N:33](OCCC(C)C)=[O:34]>O1CCCC1>[Si:7]([O:14][CH2:15][CH2:16][N:17]1[C:23]2[N:24]=[CH:25][CH:26]=[CH:27][C:22]=2[C:21]2[CH:28]=[CH:29][CH:30]=[CH:31][C:20]=2[C:19](=[N:33][OH:34])[C:18]1=[O:32])([C:10]([CH3:13])([CH3:11])[CH3:12])([CH3:9])[CH3:8]
Reactant: CC(C)CCON=O
Reactant: CC(C)(C)[Si](C)(C)OCCN1C(=O)Cc2ccccc2-c2cccnc21
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCCn1c(=O)c(=NO)c2ccccc2c2cccnc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 95.7 %

Procedure:
Add potassium 2-methylpropan-2-olate (66.1 g, 588.8 mmol) to a solution of 5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-7H-pyrido[2,3-d][3]benzazepin-6-one (155.0 g, 420.6 mmol) in tetrahydrofuran (1.6 L) at −5° C. and stir for 10 minutes. Add isoamyl nitrite (61.9 mL, 462.6 mmol) dropwise at −5° C. and stir mixture for 10 minutes. Pour over ice/water (2 L) and extract with ethyl acetate (3×200 mL). Wash combined organics with brine (200 mL), dry over sodium sulfate. Add toluene (1 L) and concentrate (×3) to obtain the title compound as a thick brown oil (160.0 g, 402.5 mmol, 96%). MS (m/z): 398 (M+1).
Reaction SMILES: C(OC)(=O)CCCCCCCCCCCCC.C(OC)(=O)CCCCCCCCCCCCCCC.[C:37]([O:56]C)(=[O:55])[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]/[CH:45]=[CH:46]\[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54].C(OC)(=O)CCCCCCC/C=C\C/C=C\CCCCC>CO>[C:37]([OH:56])(=[O:55])[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]/[CH:45]=[CH:46]\[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Agent: CCCCC/C=C\C/C=C\CCCCCCCC(=O)OC
Agent: CCCCCCCCCCCCCC(=O)OC
Agent: CCCCCCCCCCCCCCCC(=O)OC
Solvent: CO
Product: CCCCCCCC/C=C\CCCCCCCC(=O)O

Procedure:
Mixture of methyl esters, namely methyl myristate (0.5%), methyl palmitate (4.9%), methyl oleate (83.6%) and methyl linoleate (11.0%) exhibit low pour point of −21° C. This methyl esters mixture was obtained via acid-catalysed direct esterification of technical grade of oleic acid (with purity ≈80%) with methanol.