Azzindani/Open_Reaction_Data huggingface dataset:
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.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]2[O:36][C:35](=[O:37])[N:34]([CH2:38][C:39]([OH:41])=O)[C:33]=2[CH:42]=1.[C:43]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:48]=[CH:47][C:46]([C:49]([NH:57][CH3:58])([CH3:56])[CH2:50][N:51]2[CH2:55][CH2:54][CH2:53][CH2:52]2)=[CH:45][CH:44]=1.CCN(CC)CC>CN(C=O)C>[C:43]1([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:48]=[CH:47][C:46]([C:49]([N:57]([CH3:58])[C:39](=[O:41])[CH2:38][N:34]2[C:33]3[CH:42]=[C:29]([Cl:28])[CH:30]=[CH:31][C:32]=3[O:36][C:35]2=[O:37])([CH3:56])[CH2:50][N:51]2[CH2:55][CH2:54][CH2:53][CH2:52]2)=[CH:45][CH:44]=1
Reactant: CNC(C)(CN1CCCC1)c1ccc(-c2ccccc2)cc1
Reactant: O=C(O)Cn1c(=O)oc2ccc(Cl)cc21
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: CN(C(=O)Cn1c(=O)oc2ccc(Cl)cc21)C(C)(CN1CCCC1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
BOP (133 mg, 0.30 mmol) was added to a mixture containing (5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)acetic acid (68 mg, 0.30 mmol), 2-(4-biphenylyl)-N-methyl-1-(1-pyrrolidinyl)-2-propanamine (74 mg, 0.25 mmol) and Et3N (0.042 ml, 0.30 mmol) in DMF (3 ml) and the resulting mixture was stirred at room temperature for 16 h. The crude reaction mixture was purified by preparative HPLC (Xterra PrepRP 30×100 mm, 45 mL/min, A: acetonitrile B: water, PH10, A: 50 to 90% over 12 min, UV detection at 214 nm) to give 17.5 mg (13.9%) as a white solid. MS(ES) m/e 504.4 [M+H]+
Reaction SMILES: [CH:1]1[C:14]2[CH2:13][CH2:12][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]4[CH2:15][C:4]([C:5]=2[C:6]=34)=[CH:3][CH:2]=1.[Br:16]Br>C(Cl)(Cl)(Cl)Cl>[Br:16][C:2]1[CH:3]=[C:4]2[CH2:15][C:7]3[C:6]4[C:5]2=[C:14]([CH2:13][CH2:12][C:11]=4[CH:10]=[CH:9][CH:8]=3)[CH:1]=1
Reactant: c1cc2c3c(c1)Cc1cccc(c1-3)CC2
Reactant: BrBr
Solvent: ClC(Cl)(Cl)Cl
Product: Brc1cc2c3c(c1)Cc1cccc(c1-3)CC2
Temperature: 0 °C
Reaction time: 4 h
Yield: 83.3 %

Procedure:
8,9-dihydro-4H-cyclopenta[def]phenanthrene (4.0 g, 20.8 mmol) was put into a 250 ml round bottom flask (RBF), and CCl4 (100 ml) was added thereto. The reaction mixture was cooled to 0° C., and Br2 (3.3 g, 20.8 mmol) was dropwise added thereto. The reaction solution was incubated for 4 hours and a 10% NaSO3 solution was added thereto. The organic phase was separated, concentrated under a reduced pressure, and recrystallized from n-hexane to obtain 4.7 g of a 2-bromo-8,9-dihydro-4H-cyclopenta[def]phenanthrene compound.
Reaction SMILES: [C:1]1([CH2:7][C@H:8]([OH:12])[C:9]([OH:11])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)C.[Rh]>[CH:1]1([CH2:7][C@H:8]([OH:12])[C:9]([OH:11])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)[C@@H](O)Cc1ccccc1
Agent: [Rh]
Solvent: CCO
Product: O=C(O)[C@@H](O)CC1CCCCC1
Reaction time: 24 h

Procedure:
To a solution of (S)-3-phenyllactic acid (20g) in ethanol (250mL) was added 5% rhodium on alumina (2.5 g), and the reaction was shaken under 4atm H2 for 24 h. The reaction was filtered, and concentrated to give product as a white solid (≈20 g). 1H NMR (300 MHz, CDCl3) δ0.86-1.07 (m, 2H), 1.08-1.39 (m, 3H), 1.54-1.91 (m, 9H), 4.33 (dd, J=9.3, 3.6 Hz, 1H). MS(CI/NH3) m/e: (M+NH4)+ 190.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([C:23]4[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:24]=4[O:31][CH3:32])[CH2:19][CH2:18]3)=[O:16])=[CH:7][N:8]2[CH2:11][C:12]([OH:14])=O)=[CH:4][CH:3]=1.C(O[C:38](=O)[N:39]([CH2:41][CH2:42][NH2:43])C)(C)(C)C.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]([N:17]3[CH2:18][CH2:19][CH:20]([C:23]4[C:24]([O:31][CH3:32])=[CH:25][CH:26]=[CH:27][C:28]=4[O:29][CH3:30])[CH2:21][CH2:22]3)=[O:16])=[CH:7][N:8]2[CH2:11][C:12]([NH:43][CH2:42][CH2:41][NH:39][CH3:38])=[O:14])=[CH:4][CH:3]=1
Reactant: COc1cccc(OC)c1C1CCN(C(=O)c2cn(CC(=O)O)c3cc(Cl)ccc23)CC1
Reactant: CN(CCN)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CNCCNC(=O)Cn1cc(C(=O)N2CCC(c3c(OC)cccc3OC)CC2)c2ccc(Cl)cc21

Procedure:
Analogous to general procedure I, the coupling of {6-chloro-3-[4-(2,6-dimethoxy-phenyl)-piperidine-1-carbonyl]-indol-1-yl}-acetic acid (prepared herein) with (commercially available) (2-amino-ethyl)-methyl-carbamic acid tert-butyl ester gave, after treatment with TFA and neutralisation, the title compound.
Reaction SMILES: [CH3:1][S:2]([CH2:5][CH2:6][N:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[C:15]([NH2:20])[C:16]([O:18][CH3:19])=[CH:17][C:10]=2[CH2:9][CH2:8]1)(=[O:4])=[O:3].Cl[C:22]1[N:27]=[C:26]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)=[CH:31][C:30]=2[O:42][CH3:43])[C:25]([Cl:44])=[CH:24][N:23]=1>>[Cl:44][C:25]1[C:26]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)=[CH:31][C:30]=2[O:42][CH3:43])=[N:27][C:22]([NH:20][C:15]2[C:16]([O:18][CH3:19])=[CH:17][C:10]3[CH2:9][CH2:8][N:7]([CH2:6][CH2:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:13][CH2:12][C:11]=3[CH:14]=2)=[N:23][CH:24]=1
Reactant: COc1cc2c(cc1N)CCN(CCS(C)(=O)=O)CC2
Reactant: COc1cc(N2CCN(C)CC2)ccc1Nc1nc(Cl)ncc1Cl
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccc(N4CCN(C)CC4)cc3OC)n1)CCN(CCS(C)(=O)=O)CC2

Procedure:
The title compound was prepared from 3-(2-Methanesulfonyl-ethyl)-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and (2,5-Dichloro-pyrimidin-4-yl)-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenyl]-amine in an analogous manner to Example 61e. Product isolated as an off-white solid (0.052 g, 61%). MP: 138-145° C. 1H NMR (400, MHz, CDCl3, δ, ppm): 8.18 (d, 1H, J=8.6 Hz), 8.11 (s, 1H), 8.01 (d, 1H, J=1.0 Hz), 7.48 (br s, 1H), 7.43 (br s, 1H), 6.62 (s, 1H), 6.58-6.56 (m, 1H), 6.54-6.50 (m, 1H), 3.91 (s, 3H), 3.86 (s, 3H), 3.23-3.13 (m, 6H), 3.07 (s, 3H), 3.01 (t, 3H, J=6.2 Hz), 2.88-2.83 (m, 2H), 2.81-2.77 (m, 2H), 2.71-2.64 (m, 2H), 2.64-2.58 (m, 4H), 2.38 (s, 3H). MS: 630 (MH)+.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:39])=[C:9]([CH2:11][O:12][C:13]2[CH:36]=[CH:35][C:16]([CH2:17][O:18][C:19]3[C:23](/[CH:24]=[CH:25]/[C:26](=[S:28])[NH2:27])=[CH:22][N:21]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:20]=3)=[CH:15][C:14]=2[O:37][CH3:38])[N:10]=1.Br[CH2:41][C:42](=O)[C:43]([O:45][CH2:46][CH3:47])=[O:44]>C(O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:39])=[C:9]([CH2:11][O:12][C:13]2[CH:36]=[CH:35][C:16]([CH2:17][O:18][C:19]3[C:23](/[CH:24]=[CH:25]/[C:26]4[S:28][CH:41]=[C:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[N:27]=4)=[CH:22][N:21]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:20]=3)=[CH:15][C:14]=2[O:37][CH3:38])[N:10]=1
Reactant: CCOC(=O)C(=O)CBr
Reactant: COc1cc(COc2nn(-c3ccccc3)cc2/C=C/C(N)=S)ccc1OCc1nc(-c2ccco2)oc1C
Solvent: CCO
Product: CCOC(=O)c1csc(/C=C/c2cn(-c3ccccc3)nc2OCc2ccc(OCc3nc(-c4ccco4)oc3C)c(OC)c2)n1
Yield: 66 %

Procedure:
A mixture of (2E)-3-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}-2-propenethioamide (0.45 gmmol), ethyl bromopyruvate (0.20 g) and ethanol (30 mL) was heated under reflux for 1 hr. The reaction mixture was concentrated and ethyl acetate was added to the residue. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give ethyl 2-((E)-2-{3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazol-4-yl}ethenyl)-1,3-thiazole-4-carboxylate as yellow crystals (0.35 g, yield 66%) from a fraction eluted with ethyl acetate-hexane (2:1, v/v). Recrystallization from ethyl acetate-hexane gave yellow prism crystals. melting point: 156-157° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11]([OH:13])=O)[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[NH2:45][C:46]1[CH:51]=[CH:50][C:49]([N:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]2=[O:58])=[CH:48][C:47]=1[F:59]>C(#N)C>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11](=[O:13])[NH:45][C:46]2[CH:51]=[CH:50][C:49]([N:52]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]3=[O:58])=[CH:48][C:47]=2[F:59])[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1C(=O)O
Reactant: Nc1ccc(-n2ccccc2=O)cc1F
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H]1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Compound 7a (1.85 g; 6 mmol) is suspended in acetonitrile (20 ml) and N,N-diisopropyl ethyl amin (1.65 ml; 10 mmol) is added at 25° C. BOP-CL (2.46 g; 10 mmol) is added as a solid and after stirring for 30 min at 25° C. 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (1.45 g; 7 mmol) is added to the reaction mixture. The mixture is stirred for 4 d at 25° C., evaporated to dryness and dissolved in ethyl acetate (200 ml). The organic phase is washed with 2 N HCl (50 ml), with 10% aqueous Na2CO3 solution, water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 1.77 g (58.1%), ESI-MS: m/z=472 [M−H]−
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][N+:6]([O-:9])=[C:5](CC)[C:4]=1[NH2:12])C.C(O[CH:16]=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:18]([O:20][CH2:21][CH3:22])=[O:19])C>C(O)C>[CH2:21]([O:20][C:18](=[O:19])[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:16][NH:12][C:4]1[CH:5]=[N+:6]([O-:9])[CH:7]=[CH:8][CH:3]=1)[CH3:22]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: CCc1cc[n+]([O-])c(CC)c1N
Solvent: CCO
Product: CCOC(=O)C(=CNc1ccc[n+]([O-])c1)C(=O)OCC
Temperature: 130 °C
Yield: 78.4 %

Procedure:
A mixture of diethyl 3-aminopyridine 1-oxide (3.0 g, 27.3 mmol) and diethyl 2-(ethoxymethylene)malonate (11.8 g, 54.6 mmol) was heated to 130° C. under a Dean-Stark trap for 2 hours. After cooling to room temperature, the mixture was stirred with ethanol (100 mL). The solid was collected by filtration, washed with petroleum ether (100 mL) and dried in vacuo to afford the title compound (6.0 g). 1H NMR (400 MHz, MeOD) δ 8.40-8.39 (t, J=1.6 Hz, 1H), 8.36 (s, 1H), 8.01 (d, J=6.4 Hz, 1H), 7.49 (d, J=1.2 Hz, 1H), 7.46-7.44 (m, 1H), 4.22 (q, J=7.2 Hz, 2H), 4.14 (q, J=7.2 Hz, 2H), 1.08 (t, J=7.2 Hz, 6H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:21]([CH:23]=[O:24])[N:22]=3)[CH2:14][C@H:13]2[O:30][CH3:31])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].Cl([O-])=[O:33].[Na+].P([O-])(O)(O)=O.[Na+].CC(=CC)C>>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:21]([C:23]([OH:33])=[O:24])[N:22]=3)[CH2:14][C@H:13]2[O:30][CH3:31])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]
Reactant: [O-][Cl+][O-]
Reactant: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OC)C2)nc1C=O
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Product: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OC)C2)nc1C(=O)O
Yield: 100 %

Procedure:
The same operation as in Example (33c) was performed using ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained by the method described in Example (28a) (400 mg, 0.85 mmol), sodium chlorite (158 mg, 1.75 mmol), sodium dihydrogenphosphate (410 mg, 2.63 mmol) and 2-methyl-2-butene (0.55 mL, 5.20 mmol), to obtain 439 mg of the title compound (100%).
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[NH:9]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[CH:11]=[N:10]1>O1CCCC1>[Br:1][C:13]1[C:14]([OH:18])=[CH:15][CH:16]=[C:17]2[C:12]=1[CH:11]=[N:10][NH:9]2
Reactant: Oc1ccc2[nH]ncc2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: C1CCOC1
Product: Oc1ccc2[nH]ncc2c1Br
Temperature: 25 °C
Reaction time: 14 h
Yield: 90.6 %

Procedure:
N-bromosuccinimide (1.06 g, 5.96 mmol) was added to a solution of the 1H-indazol-5-ol (800 mg, 5.96 mmol) obtained in Reference Example 4 in tetrahydrofuran (20 ml) at room temperature. The resulting mixture was stirred for 14 hours while being maintained at room temperature. The mixture was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 4-bromo-1H-indazol-5-ol (1.15 g, 91%).
Reaction SMILES: [CH2:1]([C:4]1[CH:16]=[CH:15][C:7]([CH2:8][NH:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:6][CH:5]=1)[CH2:2][CH3:3].[CH2:17]([C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](O)=[O:28])=[CH:22][CH:21]=1)[CH2:18][CH3:19].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.S([O-])([O-])(=O)=O.[Mg+2]>C(Cl)Cl>[CH2:1]([C:4]1[CH:16]=[CH:15][C:7]([CH2:8][N:9]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[C:27](=[O:28])[CH2:26][C:23]2[CH:24]=[CH:25][C:20]([CH2:17][CH2:18][CH3:19])=[CH:21][CH:22]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3]
Reactant: CCCc1ccc(CNCC(=O)OC)cc1
Reactant: CCCc1ccc(CC(=O)O)cc1
Agent: O=S(=O)([O-])[O-]
Agent: On1nnc2ccccc21
Agent: [Mg+2]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CCCc1ccc(CC(=O)N(CC(=O)OC)Cc2ccc(CCC)cc2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 80.3 %

Procedure:
Methyl 2-((4-propylbenzyl)amino)acetate (24.5 mg, 0.0983 mmol) and 2-(4-propylphenyl)acetic acid (17.5 mg, 0.0983 mmol) were dissolved in 1 mL of well-dried DCM under argon condition and then EDC (56.5 mg, 0.295 mmol), HOBt (39.8 mg, 0.295 mmol) and DIPEA (84.3 μL, 0.491 mmol) were added and the reaction mixture was stirred for 20 hours at room temperature. Upon completion of the reaction, the reaction was terminated by adding 3 mL of water, and the reaction mixture was extracted with DCM (3 mL×4). The organic layer thus obtained was treated with anhydrous magnesium sulfate to remove water. The precipitate was filtered out and the resulting solution was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 31.1 mg (0.0789 mmol, 80%) of the desired compound.
Reaction SMILES: [N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=1)[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1.CC(C)([O-])C.[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.O>[O:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[O:18][C:17]1[CH:16]=[C:15]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH:27]=[CH:26][CH:25]=1
Reactant: Brc1cccc(OC2CCCCO2)c1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(c2cccc(OC3CCCCO3)c2)CC1
Yield: 101.5 %

Procedure:
A mixturte of tert-butyl piperazine-1-carboxylate (2.94 g, 15.8 mmol), 2-(3-bromophenoxy)tetrahydropyran (3.69 g, 14.4 mmol), palladium acetate (64 mg, 0.29 mmol), BINAP (285 mg, 0.43 mmol) and sodium tert-butoxide (1.8 g, 18.7 mmol) in toluene (40 ml) was refluxed under a nitrogen atmosphere for 2 hours. Ethyl acetate and water were added to the reaction mixture, which was stirred for a while. The insoluble substances were removed by filtration through Celite, and the filtrate was then extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica-gel column chromatography (n-hexane/ethyl acetate=20/1) to afford tert-butyl 4-[3-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate (5.3 g, yield 99%) as a colorless oil.
Reaction SMILES: N(C1C(C2C=C(Cl)C=CC=2)=CC=CC=1C([O-])=O)=NC1C(C2C=C([Cl:18])C=CC=2)=CC=CC=1C([O-])=O.[C:35]([O:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[N+:50]([O-])=O)(=O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>>[Cl:18][C:48]1[CH:47]=[CH:46][C:45]2[N:50]=[C:35]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[O:43][C:44]=2[CH:49]=1
Reactant: O=C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Reactant: O=C([O-])c1cccc(-c2cccc(Cl)c2)c1N=Nc1c(C(=O)[O-])cccc1-c1cccc(Cl)c1
Product: Clc1ccc2nc(-c3ccccc3)oc2c1

Procedure:
When the above procedure is followed substituting an equivalent amount of 2,2'-azobis(5-chlorophenyl benzoate) for the o-nitrophenyl benzoate, 6-chloro-2-phenylbenzoxazole is obtained.
Reaction SMILES: [OH:1][C:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][C:5](=[O:8])[CH:4]=[CH:3]1.[C:15](OC(=O)C)(=[O:17])[CH3:16].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1.CCOCC>[C:15]([O:1][C:2]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:3]=[CH:4][C:5](=[O:8])[CH:6]=[CH:7]1)(=[O:17])[CH3:16]
Reactant: CC(=O)OC(C)=O
Reactant: O=C1C=CC(O)(c2ccccc2)C=C1
Agent: CN(C)c1ccncc1
Solvent: CCOCC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)OC1(c2ccccc2)C=CC(=O)C=C1
Temperature: 25 °C
Reaction time: 24 h
Yield: 62 %

Procedure:
To 4-hydroxy-4-phenyl-2,5-cyclohexadienone (0.335 g, 1.8 mmol), acetic anhydride (0.276 g, 2.7 mmol, 1.5 equivalents) and triethylamine (0.273 g, 2.7 mmol, 1.5 equivalents) dissolved in dichloromethane (20 mL) was added 4-dimethylaminopyridine (DMAP) (0.044 g, 0.36 equivalents). The reaction mixture was stirred for 24 hours at room temperature, washed with 1 M HCl (20 mL) then saturated sodium hydrogen carbonate solution (2×20 mL) and the organic layer dried over magnesium sulphate. Removal of the solvent in vacuo gave an oil which was dissolved in ether, filtered and the solvent removed in vacuo to gave the title compound as a white solid. The yield was 62%; mp 100–101° C. (lit. 106–109° C.); 1H NMR (CDCl3) δ 7.48–7.36 (5H, m, ArH); 6.99 (2H, d, J 19.2 Hz, H-3, H-5); 6.36 (2H, d, J 10.2 Hz, H-2, H-6); 2.22 (3H, s, O2CCH3).
Reaction SMILES: S(=O)(=O)(O)O.[N+:6]([C:9]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])([O-:8])=[O:7].[CH3:22]O>>[N+:6]([C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:14][C:10]=1[C:11]([O:13][CH3:22])=[O:12])([O-:8])=[O:7]
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 99 %

Procedure:
Add concentrated sulfuric acid (120 mL) dropwise to a solution of 2-nitro-4-trifluoromethylbenzoic acid (200 g, 850 mmol) in methanol (2 L) at room temperature under nitrogen and heat the mixture at reflux for 48 h. Cool the solution to room temperature and remove most of the solvent by evaporation at 45° C. under reduced pressure. Pour the turbid residue onto ice/water (2 L) and extract with ethyl acetate (2×1 L). Wash the combined organic extracts with brine (1 L), dry over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure to provide the title compound as a yellow oil (212.2 g, >99%). 1H NMR (300 MHz, CDCl3) δ 8.21 (s, 1H), 7.95 (d, J=1.13 Hz, 1H), 7.90 (s, 1H), 3.97 (s, 3H).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:9]([CH2:10][O:11]C(=O)C2C=CC=CC=2)[O:8][C@@H:7]([N:20]2[CH:28]=[C:26]([CH3:27])[C:24](=[O:25])[NH:23][C:21]2=[O:22])[C@H:6]1[F:29])(=O)C>N>[F:29][C@H:6]1[C@H:5]([OH:4])[C@@H:9]([CH2:10][OH:11])[O:8][C@H:7]1[N:20]1[CH:28]=[C:26]([CH3:27])[C:24](=[O:25])[NH:23][C:21]1=[O:22]
Reactant: CC(=O)O[C@H]1[C@H](F)[C@H](n2cc(C)c(=O)[nH]c2=O)O[C@@H]1COC(=O)c1ccccc1
Agent: N
Product: Cc1cn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2F)c(=O)[nH]c1=O
Reaction time: 16 h
Yield: 83.3 %

Procedure:
1-(3-O-Acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (150 mg) is dissolved in saturated methanolic ammonia (15 ml), and the mixture left standing for 16 hours. The solvent is removed by evaporation in vacuo, and the residue crystallized from water to give 80 mg of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine, m.p. 185°-185.5°.
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(CC)CC)C.[CH3:13][C:14]1([CH3:31])[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[C:20]2[CH:19]=[C:18]([CH:26]=[CH:27][C:28](Cl)=[O:29])[CH:17]=[CH:16][C:15]1=2.O>C1COCC1>[CH3:5][O:4][N:3]([CH3:2])[C:28](=[O:29])/[CH:27]=[CH:26]/[C:18]1[CH:17]=[CH:16][C:15]2[C:14]([CH3:31])([CH3:13])[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[C:20]=2[CH:19]=1
Reactant: CC1(C)CCC(C)(C)c2cc(C=CC(=O)Cl)ccc21
Reactant: CNOC
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CON(C)C(=O)/C=C/c1ccc2c(c1)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 6 h

Procedure:
727 mg (7.45 mmol) of N,O-dimethylhydroxyl-amine hydrochloride, 10 ml of THF and 2.3 ml (16.4 mmol) of triethylamine are introduced into a three-necked flask under a stream of nitrogen. A solution of 2.06 g (7.45 mmol) of 3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)acryloyl chloride prepared in Example 1(c) in 20 ml of THF is added dropwise and the mixture is stirred at room temperature for six hours. The reaction medium is poured into water and extracted with ethyl acetate, and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a mixture of heptane and ethyl acetate (80/20). After evaporating the solvents, 1 g (45%) of (E)-N-methoxy-N-methyl-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)acrylamide is collected in the form of an oil.
Reaction SMILES: [CH3:1][CH:2]([CH2:5][C:6]1[CH:10]([C:11]([CH3:13])=[CH2:12])[CH2:9][CH2:8][C:7]=1[CH3:14])[CH2:3][OH:4]>[Ni].CO>[CH3:1][CH:2]([CH2:5][C:6]1[CH:10]([CH:11]([CH3:13])[CH3:12])[CH2:9][CH2:8][C:7]=1[CH3:14])[CH2:3][OH:4]
Reactant: C=C(C)C1CCC(C)=C1CC(C)CO
Agent: [Ni]
Solvent: CO
Product: CC1=C(CC(C)CO)C(C(C)C)CC1
Yield: 93.9 %

Procedure:
9.7 g of 2-methyl-3-(2-methyl-5-isopropenyl-cyclopent-1-en-1-yl)-propanol were catalytically hydrogenated in the presence of traces of Raney nickel in methanol. 1130 ml of hydrogen were absorbed and the reaction mixture was filtered, whereupon the clear filtrate was evaporated to give 9.2 g of 2-methyl-3-(2-methyl-5-isopropyl-cyclopent-1-en-1-yl)-propanol;
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[N+:12]([O-])([OH:14])=[O:13].[N+]([O-])(O)=O.C(O)(=O)C>C(O)(=O)C>[N+:12]([C:7]1[CH:6]=[C:5]([CH2:8][C:9]([OH:11])=[O:10])[CH:4]=[CH:3][C:2]=1[OH:1])([O-:14])=[O:13]
Reactant: O=C(O)Cc1ccc(O)cc1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: O=C(O)Cc1ccc(O)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In a first step, carried out according to Humel in Synth. Commun. 15, pages 1081-88 (1985), to a magnetically stirred solution of 100 g (0.65,mole) of 4-hydroxyphenyl acetic acid in 250 ml of glacial acetic acid was added dropwise a mixture of 40 ml of nitric acid (1.4 specific gravity) and 60 ml glacial acetic acid. The glacial acetic acid was warmed to about 45° C. to completely dissolve the 4-hydroxyphenyl acetic acid. Following addition of the nitric acid/acetic acid mixture, stirring of the resulting mixture was continued for one hour at 25° C. and then the flask was chilled in ice water for one hour. The resulting crystals were washed with cold water and air-dried at room temperature, the reaction providing 65% of the theoretical yield of 3-nitro 4-hydroxyphenyl acetic acid.