Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].C(Cl)(=O)C([Cl:16])=O>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([Cl:16])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)Cc1ccc(Cl)c(Cl)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)Cc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 95.6 %

Procedure:
3,4-Dichlorophenylacetic acid (76.8 g) was dissolved in dry dichloromethane (300 ml) and oxalyl chloride (52 g, 36 ml) was added to the solution obtained in one portion. The reaction mixture was protected from atmospheric moisture with a calcium chloride guard tube and stirred mechanically whilst dimethylformamide (3 drops) was added. The solution was stirred at ambient temperature for 18 hours and then evaporated under reduced pressure to give a yellow oil. Distillation in vacuo afforded 80.0 g of 3,4-dichlorophenylacetyle chloride, b.pt 97°-100°/0.6 mm, as a viscous pale yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CS([C:20]1[N:25]=[CH:24][C:23]2=[CH:26][CH:27]=[C:28]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[N:22]2[N:21]=1)=O.[F-].[Cs+].C(N(CC)C(C)C)(C)C>C(O)(C)(C)C>[OH:16][CH2:15][CH2:14][N:11]1[CH2:10][CH2:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:20]3[N:25]=[CH:24][C:23]4=[CH:26][CH:27]=[C:28]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=5[N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[N:22]4[N:21]=3)=[CH:7][CH:6]=2)[CH2:13][CH2:12]1
Reactant: CN(c1ccccc1-c1ccc2cnc(S(C)=O)nn12)S(C)(=O)=O
Reactant: Nc1ccc(N2CCN(CCO)CC2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)(C)O
Product: CN(c1ccccc1-c1ccc2cnc(Nc3ccc(N4CCN(CCO)CC4)cc3)nn12)S(C)(=O)=O
Temperature: 120 °C

Procedure:
Into a 8-dram vial, 2-[4-(4-Amino-phenyl)-piperazin-1-yl]-ethanol (0.134 g, 0.604 mmol), N-[2-(2-Methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide (0.100 g, 0.274 mmol), Cesium fluoride (0.104 g, 0.686 mmol), N,N-Diisopropylethylamine (0.1051 mL, 0.6036 mmol) and tert-Butyl alcohol (1.50 mL) were added. The reaction was heated at 120° C. overnight. LCMS suggested presence of desired product. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give N-[2-(2-{4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide as a yellow solid (48 mg, 34%). LCMS (E/I+) 522.16 (M+H). NMR 1H (DMSO-d6)-9.15 (bs, 1H), 9.24 (s, 1H), 8.94 (s, 1H), 8.02 (d, 1H, J=7.91 Hz), 7.66 (d, 1H, J=7.34 Hz), 7.47-7.62 (m, 4H), 6.98 (d, 1H, J=4.52 Hz), 6.93 (d, 1H, J=4.52), 6.87 (d, 1H, J=8.47 Hz), 3.77 (bs, 2H), 3.70 (d, 2H, J=12.98 Hz), 3.58 (d, 2H, J=12.86 Hz), 3.13-3.30 (m, 2H), 3.08 (s, 1H), 2.97 (t, 2H, J=12.42 Hz), 2.89 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:27]([O:29][C:30](Cl)(Cl)Cl)=[O:28].[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36]CO.C(N(CC)CC)C>O1CCOCC1>[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36][CH2:30][O:29][C:27](=[O:28])[NH:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:14](=[O:15])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]([F:25])([F:24])[F:23])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)CCO
Reactant: Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)(C)CCOC(=O)Nc1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1
Temperature: 25 °C
Yield: 11 %

Procedure:
To a solution of [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethyl-phenyl)methanone (200 mg, 0.57 mmol) in 10 mL of dioxane was added trichloromethyl chloroformate (112.7 mg, 0.57 mmol) and stirred at ambient temperature. After 30 minutes 3,3-dimethylbutan-1-ol (175.5 mg, 1.71 mmol) and triethylamine (57.6 mg, 0.57 mmol) were added and the temperature was raised to 80° C. The mixture was stirred for 3 h under N2, and then concentrated. The residue was dissolved in dichloromethane (100 mL), and washed with 1 N HCl (2×20 mL), saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL). The combined organic extract was dried over anhydrous Na2SO4, concentrated, and then purified by column chromatography eluted with hexane:ethyl acetate (1:2). The product was obtained as a white solid (30 mg, 11% yield). 1H NMR (300 MHz, DMSO-d6) δ 10.38, 7.89, 7.83, 7.77, 7.67, 7.54, 7.47, 4.14, 3.10-3.90, 1.55, 0.95.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[I:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22]O)=[C:18]([CH3:24])[CH:17]=1>>[I:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)=[C:18]([CH3:24])[CH:17]=1
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Reactant: Cc1cc(I)ccc1CO
Product: Cc1cc(I)ccc1COc1ccnn1-c1cc(C#N)ccn1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (4-iodo-2-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.33 (3H, s), 5.15 (2H, s), 5.76 (1H, d, J=1.6 Hz), 7.14 (1H, d, J=8.0 Hz), 7.39 (1H, dd, J=1.6 Hz, 5.2 Hz), 7.55-7.59 (3H, m), 8.00 (1H, s), 8.66 (1H, d, J=5.2 Hz). [M+H] Calc'd for C17H13IN4O, 417; Found, 417.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)=[CH:5][CH:4]=1.[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[C:33]([CH3:34])=[C:32]([CH:35]=O)[NH:31][C:30]=2[CH3:37])=[O:28])[CH2:23][CH2:22][CH2:21][CH2:20]1>C(O)C.N1CCCCC1>[N:19]1([CH2:24][CH2:25][NH:26][C:27]([C:29]2[C:33]([CH3:34])=[C:32]([CH:35]=[C:11]3[C:10]4[C:14](=[CH:15][CH:16]=[CH:17][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[NH:13][C:12]3=[O:18])[NH:31][C:30]=2[CH3:37])=[O:28])[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: COc1ccc(-c2cccc3c2CC(=O)N3)cc1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)NCCN1CCCC1
Solvent: CCO
Solvent: C1CCNCC1
Product: COc1ccc(-c2cccc3c2C(=Cc2[nH]c(C)c(C(=O)NCCN4CCCC4)c2C)C(=O)N3)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 71 %

Procedure:
To a solution of 4-(4-methoxy-phenyl)-1,3-dihydro-indol-2-one (59.8 mg, 0.25 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (68.5 mg, 0.25 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 5-[4-(4-Methoxy-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide as a yellow solid (86 mg, 71%).
Reaction SMILES: [N:1]1[C:10]2[CH:9]([NH:11][CH2:12][C:13]3[CH:29]=[CH:28][C:16]([CH2:17][NH:18][S:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)(=[O:21])=[O:20])=[CH:15][CH:14]=3)[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:30][Si:31]([CH3:48])([CH3:47])[CH2:32][CH2:33][O:34][CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[CH:45]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[N:1]1[C:10]2[CH:9]([N:11]([CH2:12][C:13]3[CH:14]=[CH:15][C:16]([CH2:17][NH:18][S:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)(=[O:20])=[O:21])=[CH:28][CH:29]=3)[CH2:45][C:37]3[N:36]([CH2:35][O:34][CH2:33][CH2:32][Si:31]([CH3:30])([CH3:47])[CH3:48])[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=3)[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(NCc1ccc(CNC2CCCc3cccnc32)cc1)c1ccccn1
Reactant: C[Si](C)(C)CCOCn1c(C=O)nc2ccccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: C[Si](C)(C)CCOCn1c(CN(Cc2ccc(CNS(=O)(=O)c3ccccn3)cc2)C2CCCc3cccnc32)nc2ccccc21
Yield: 40.8 %

Procedure:
Using general procedure B: Reaction of pyridine-2-sulfonic acid 4-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-benzylamide (AMD9426) (150 mg, 0.37 mmol), 1-(2-trimethylsilanyl-ethoxymethyl)-1 H-benzoimidazole-2-carbaldehyde (102 mg, 0.37 mmol), and NaBH(OAc)3 (233 mg, 1.10 mmol) for 1 h at room temperature followed by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH 198:1:1) gave the title compound (101 mg, 41%) as a yellow foam. 1H NMR (300 MHz, CD3OD) δ 0.00 (s, 9H), 0.75 (dd, 2H, J=8.1, 8.1 Hz), 1.58-1.75 (m, 2H), 2.22 (br s, 2H), 2.66-2.85 (m, 2H), 3.25 (dd, 2H, J=8.1, 8.1 Hz), 3.66 (d, 1H, J=14.1 Hz), 3.78 (d, 1H, J=14.1 Hz), 4.02 (d, 1H, J=6.0 Hz), 4.06-4.16 (m, 1H) 4.20 (brs, 2H), 4.81 (br s, 1H), 5.68 (d, 1H, J=12.0 Hz), 5.91 (d, 1H, J=12.0 Hz), 6.92 (d, 2H, J=7.8 Hz), 7.06 (dd, 1H, J=7.5, 4.8 Hz), 7.17-7.23 (m, 4H), 7.30-7.35 (m, 2H), 7.45 (ddd, 1H, J=7.5, 4.5, 1.1 Hz), 7.61-7.64 (m, 1H), 7.87 (ddd, 1H, J=7.8, 7.8,1.7 Hz), 7.98 (d, 1H, J=7.8 Hz), 8.55 (d, 1H, J=3.6 Hz), 8.68 (d, 1H, J=3.9 Hz).ES-MS m/z 669 (M+H).
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2].C([O:32]O)(C)(C)C>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Cr]>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][C:9](=[O:32])[C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1
Reactant: CC(C)(C)OO
Agent: [Cr]
Agent: [C-]#[O+]
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC(=O)[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1

Procedure:
A second method of preparing βAET has been developed which also used 3β,17β diacetoxyandrost-5-ene as a starting material as before. This compound was oxidized with t-butylhydroperoxide in the presence of chromium hexacarbonyl (Cr(CO)6) to form 3β,17β-diacetoxyandrost-5-en-7-one as described by Pearson [Pearson, et al., J. Chem Soc. Perkin Trans. I, 267 (1985)]. The enone formed then was reduced with triisobutylaluminum (TIBA) to give the acetylated 7β-hydroxy (I) product.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[C:31]([O:35][C:36](=[O:39])[CH2:37][NH2:38])([CH3:34])([CH3:33])[CH3:32]>CN(C=O)C>[C:31]([O:35][C:36](=[O:39])[CH2:37][NH:38][C:8]([C:3]1[C:2]([OH:1])=[CH:7][CH:6]=[CH:5][N:4]=1)=[O:10])([CH3:34])([CH3:33])[CH3:32]
Reactant: O=C(O)c1ncccc1O
Reactant: CC(C)(C)OC(=O)CN
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)CNC(=O)c1ncccc1O
Temperature: 25 °C
Reaction time: 72 h
Yield: 21.5 %

Procedure:
To a solution of 3-hydroxypicolinic acid (0.20 g, 1.44 mmol) in DMF (5 mL) at 0° C. under N2 is added diisopropylethylamine (DIPEA) (0.75 ml, 4.3 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (EDCI) (0.412 g, 2.9 mmol) and 1-hydroxybenzo-triazole (HOBt) (0.019 g, 0.14 mmol). The resulting mixture is stirred for 5 min before glycine tert-butyl ester HCl (0.36 g, 2.9 mmol) is introduced. The resulting solution is stirred at room temperature for 3 days then concentrated under reduced pressure. The reaction mixture is diluted with EtOAc then washed with 1M HCl, sat. NaCl, and the organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to a crude oil that is purified over silica (EtOAc/heptane 1:4) to afford 0.078 g (22% yield) of the desired compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.80 (1H, s), 8.39 (1H, br s), 8.02 (1H, dd, J=4.4, 1.5 Hz), 7.27 (1H, dd, J=8.8, 4.4 Hz), 7.25 (1H, dd, J=8.4, 1.5 Hz), 4.06 (2H, d, J=5.5 Hz), 1.44 (9H, s). HPLC-MS: m/z 197 [M-tBu]+.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]([CH:17]3[CH2:21][CH2:20][CH2:19][N:18]3[CH2:22][C:23]([C:25]3[S:26][CH:27]=[CH:28][CH:29]=3)=O)[CH:14]=[CH:15][CH:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N>CO.C(Cl)Cl>[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:14]([C@H:23]([C:25]4[S:26][CH:27]=[CH:28][CH:29]=4)[CH2:22][N:18]4[CH2:19][CH2:20][CH2:21][C@H:17]43)=[CH:15][CH:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(CN1CCCC1c1cccc(OCCCN2CCCCC2)c1)c1cccs1
Agent: N
Solvent: ClCCl
Solvent: CO
Product: c1csc([C@@H]2CN3CCC[C@H]3c3cc(OCCCN4CCCCC4)ccc32)c1
Yield: 85 %

Procedure:
2-{2-[3-(3-Piperidin-1-yl-propoxy)-phenyl]-pyrrolidin-1-yl}-1-thiophen-2-yl-ethanone. Prepared as described in Example 8, Step 1, on a 3.47 mmol scale, to give 1.24 g (85%) of the desired product as an oil after chromatography (NH3 in MeOH/CH2Cl2). MS: exact mass calcd for C24H32N2O2S, 412.2; m/z found, 413.6 [M+H]+. 1H NMR (MeOH-d4): 7.75 (m, 2H) 7.18 (t, J=8.0, 1H), 7.09 (dd, J=4.0, 5.0, 1H), 7.0 (m, 1H), 6.94 (d, J=7.6, 1H), 6.77 (m, 1H), 4.88 (s, 1H), 3.96 (m, 2H), 3.88 (d, J=16.4, 1H), 3.47 (d, J=8.8, 1H), 3.42 (d, J=16.0, 1H), 3.37 (m, 1H), 3.34 (s, 2H), 2.43 (m, 7H), 2.18 (m, 1H), 1.94 (m, 3H), 1.86 (m, 1H), 1.76 (m, 1H), 1.59 (m, 4H), 1.45 (br m, 2H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([F:14])([CH3:13])[CH:7](O)[C:8]([O:10][CH3:11])=[O:9].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:27][O:28][C:29]1[CH:34]=[C:33]([O:35][CH3:36])[N:32]=[C:31]([SH:37])[N:30]=1.C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([F:14])([CH3:13])[CH:7]([S:37][C:31]1[N:30]=[C:29]([O:28][CH3:27])[CH:34]=[C:33]([O:35][CH3:36])[N:32]=1)[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)C(O)C(C)(F)c1cccs1
Reactant: COc1cc(OC)nc(S)n1
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C(Sc1nc(OC)cc(OC)n1)C(C)(F)c1cccs1
Temperature: 0 °C

Procedure:
5.5 g (25 mmol) of methyl 3-(2-thienyl)-3-fluoro-2-hydroxybutyrate (Compound 1.1) are dissolved in 50 ml of dichloromethane, 3 g (30 mmol) of triethylamine are added, and 3.2 g (28 mmol) of methanesulfonyl chloride are added dropwise with stirring. The mixture is stirred for 2 hours at room temperature, washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue is taken up in dimethylformamide (DMF), and this is added dropwise at 0° C. to a suspension of 12.9 g (75 mmol) of 4,6-dimethoxypyrimidine-2-thiol and 8.4 g (100 mmol) of sodium hydrogen carbonate in 100 ml of DMF. After the mixture has been stirred for 2 hours at room temperature and for a further 2 hours at 60° C., the mixture is poured into 1 l of ice-water, and the precipitate which has formed is filtered off with suction. After drying, 2.5 g of a white powder remain.
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=O)[CH2:16][S:17][C:18]#[N:19])=[CH:11][CH:10]=1.[Cl-].[CH2:22]([O:24][C:25]([C:27]1([NH3+:30])[CH2:29][CH2:28]1)=[O:26])[CH3:23]>C(O)C>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]=[C:18]([NH:30][C:27]3([C:25]([O:24][CH2:22][CH3:23])=[O:26])[CH2:29][CH2:28]3)[S:17][CH:16]=2)=[CH:11][CH:10]=1
Reactant: CCOC(=O)C1([NH3+])CC1
Reactant: N#CSCC(=O)c1ccc(Br)cc1
Agent: [Cl-]
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)C1(Nc2nc(-c3ccc(Br)cc3)cs2)CC1
Temperature: 65 °C
Reaction time: 96 h
Yield: 35.7 %

Procedure:
Triethylamine (3.1 mL, 22.3 mmol) was added under nitrogen to a mixture of 2-(4-bromophenyl)-2-oxoethyl thiocyanate (5.2024 g, 20.3 mmol), prepared in step 1 of Example 1, and 1-ethoxycarbonyl-cyclopropyl-ammonium chloride (3.7001 g, 22.3 mmol), prepared in the previous step, in 400 mL of absolute ethanol. After the addition, the reaction was stirred at 65° C. for 4 days. The reaction was concentrated under reduced pressure to remove the ethanol. The residue was taken up in methylene chloride, applied to a Biotage FLASH 25+™ cartridge and the methylene chloride allowed to evaporate. Purification of the residue on the samplet on a Horizon™ Flash Collector (the Biotage FLASH 25+™ cartridge) using a linear gradient of 5% ethyl acetate-hexane to 100% ethyl acetate gave ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropane carboxylate (2.66 g, 36%) as a light yellow solid, mp 152-154° C.; MS m/z 367.
Reaction SMILES: C(O)(=O)C.[C:5]([NH:8][C:9]1[C:10]([F:31])=[CH:11][C:12]([N+:28]([O-])=O)=[C:13]([CH:27]=1)[O:14][C:15]1[CH:26]=[CH:25][CH:24]=[CH:23][C:16]=1[O:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])(=[O:7])[CH3:6]>[Fe].O>[C:5]([NH:8][C:9]1[C:10]([F:31])=[CH:11][C:12]([NH2:28])=[C:13]([CH:27]=1)[O:14][C:15]1[CH:26]=[CH:25][CH:24]=[CH:23][C:16]=1[O:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])(=[O:7])[CH3:6]
Reactant: COC(=O)COc1ccccc1Oc1cc(NC(C)=O)c(F)cc1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)COc1ccccc1Oc1cc(NC(C)=O)c(F)cc1N
Temperature: 80 °C
Yield: 72.8 %

Procedure:
To a mixture of 40 ml of acetic acid and 40 ml of water was added 2.2 g of iron powder, and the temperature was increased to 80° C. To the mixture was added 3.0 g of methyl [2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate, and the mixture was heated at reflux for 30 minutes. The mixture was then poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and then concentrated to give 2.01 g of methyl [2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate.
Reaction SMILES: [CH2:1]1[O:11][C:10]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=2[O:2]1.[CH3:12][N:13]([CH3:23])[C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18].C(N1C2C=CC(C3C4C(=CC(N(C)C)=CC=4)C(=O)O3)=CC=2C2C1=CC=CC=2)C>C(OC(=O)C)(=O)C>[CH2:1]1[O:11][C:10]2[CH:9]=[CH:8][C:5]([CH:6]3[C:20]4[C:16](=[CH:15][C:14]([N:13]([CH3:23])[CH3:12])=[CH:22][CH:21]=4)[C:17](=[O:18])[O:7]3)=[CH:4][C:3]=2[O:2]1
Reactant: CN(C)c1cccc(C(=O)O)c1
Reactant: O=Cc1ccc2c(c1)OCO2
Agent: CCn1c2ccccc2c2cc(C3OC(=O)c4cc(N(C)C)ccc43)ccc21
Solvent: CC(=O)OC(C)=O
Product: CN(C)c1ccc2c(c1)C(=O)OC2c1ccc2c(c1)OCO2
Yield: 6.1 %

Procedure:
Following a procedure similar to that described in Example 1, part A above, 7.5 g of 3,4-(methylenedioxy)benzaldehyde and 9.1 g of 3-dimethylaminobenzoic acid were interacted in acetic anhydride to obtain 0.9 g of 3-(3,4-methylenedioxyphenyl)-6-dimethylaminophthalide (Formula II: R=CH3 ; X=H; Y=1-[3,4-(OCH2O)C6H3 ]) a light yellow solid melting over the range 134°-143° C.
Reaction SMILES: [CH2:1]([N+:3]1([O-])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[C:4]1=[O:14])[CH3:2].C[Si]([C:20]#[N:21])(C)C.CN(C)C(Cl)=O>[N+](CC)([O-])=O>[CH2:1]([N:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:20]#[N:21])[CH:9]=2)[C:4]1=[O:14])[CH3:2]
Reactant: CC[N+]1([O-])CCN(c2ccncc2)C1=O
Reactant: C[Si](C)(C)C#N
Agent: CN(C)C(=O)Cl
Solvent: CC[N+](=O)[O-]
Product: CCN1CCN(c2ccnc(C#N)c2)C1=O
Temperature: 25 °C
Reaction time: 20 h
Yield: 29.1 %

Procedure:
1-Ethyl-3-(4-pyridyl)-2-imidazolidinone N-oxide (0.56 g, 2.7 mmol) was dissolved in nitroethane (20 ml), and trimethylsilyl cyanide (0.55 g, 5.5 mmol) and N,N-dimethylcarbamoyl chloride (0.44 g, 4.1 mmol) were added thereto. The mixture was stirred at room temperature for 20 hrs. The solvent was evaporated, and the residue was subjected to a silica gel column chromatography. The fractions eluted with ethyl acetate-hexane (5:1, v/v) were collected, concentrated and recrystallized from tetrahydrofuran-hexane to give the titled compound (0.17 g, 29%) as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5](OC)=O)[C:3]=1[OH:12].[C:13]([O-])([O-])=O.[K+].[K+].Br[CH2:20][C:21]([O:23][CH3:24])=[O:22]>CC(C)=O>[CH3:13][O:12][C:3]1[C:4](=[CH:9][CH:10]=[CH:11][C:2]=1[Cl:1])[CH:5]=[CH:20][C:21]([O:23][CH3:24])=[O:22]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)c1cccc(Cl)c1O
Reactant: COC(=O)CBr
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)C=Cc1cccc(Cl)c1OC
Reaction time: 18 h
Yield: 116.7 %

Procedure:
A mixture of 3-chlorosalicylic acid (20.2 g, 0.117 mol), Na2SO4 (5.0 g, 0.035 mol), MeOH (100 mL), and saturated methanolic HCl (40 mL) was heated under reflux for 2 days. The mixture was filtered, concentrated, and partitioned between ether and H2O. The organic phase was washed with saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a yellow oil (17.4 g). A mixture of methyl 3-chlorosalicylate (17.4 g, 0.093 mol), K2CO3 (12.9 g, 0.093 mol), and acetone (100 mL) was heated for 10 minutes. Additional acetone (100 mL) and methyl bromoacetate (14.3 g, 0.093 mol) were added and heating was continued for 18 hours. The mixture was cooled, concentrated, and partitioned between ether and H2O. The organic phase was dried (MgSO4) and concentrated to give a pale yellow oil (24.6 g, 80%).
Reaction SMILES: C([Li])CCC.C1C2CC3C(=CC=CC=3)C=2C=CC=1.C(C(CCCC)CBr)C.[CH2:28]([CH:30]([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:31][CH:32]1[C:44]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:38]2[C:33]1=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH3:29].Cl[CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH3:59]>CCCCCC.O1CCCC1.O>[CH2:28]([CH:30]([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:31][C:32]1([CH2:50][CH2:51][O:52][CH2:53][CH2:54][O:55][CH2:56][CH2:57][O:58][CH3:59])[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:38]=2[C:39]2[C:44]1=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH3:29]
Reactant: COCCOCCOCCCl
Reactant: CCCCC(CC)CC1c2ccccc2-c2ccccc21
Agent: CCCCC(CC)CBr
Agent: [Li]CCCC
Agent: c1ccc2c(c1)Cc1ccccc1-2
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: CCCCC(CC)CC1(CCOCCOCCOC)c2ccccc2-c2ccccc21
Temperature: -7.5 °C
Reaction time: 1 h

Procedure:
7.69 g of butyllithium dissolved in 48 ml of hexane was slowly added during 5 minutes into 20.0 g of fluorene dissolved in 150 ml of anhydrous tetrahydrofuran at -50° C. under nitrogen protection. The mixture was stirred at -30 to 15° C. for 1 hour before it was cooled again to -40 to -50° C. Then, 23.17 g of 2-ethylhexyl bromide was added in 5 minutes. The mixture was subsequently stirred for 2 hours while the temperature was gradually increased to 22° C. The main product in the solution was 9-(2-ethylhexyl)-fluorene as detected by GC-MS. This solution was then cooled to -50° C., and 7.7 g of butyllithium dissolved in 48 ml of hexane was slowly added in 5 minutes under nitrogen protection. The mixture was stirred at -30~15° C. for 1 hour before it was cooled again to -40 to -50° C. Then, 23.75 g of 1-(2-chloroethoxy)-2-(2-methoxyethoxy)-ethane was added in 5 minutes. The mixture was subsequently stirred for 15 hours at 22° C., dispersed in water, and extracted with ether. The etheral solution was washed with water and brine, dried with magnesium sulfate, and evaporated. The residue was distilled to collect 45.5 g (89%) of colorless liquid at 190° C./0.12 mm Hg. MS (m/z): 424 (M+), 277, 205, 191, 178, 165, 133, 103, 59.
Reaction SMILES: [C-:1]#[N:2].[K+].[N+]([C:7]1[CH:20]=[CH:19][C:10]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])=[CH:9][CH:8]=1)([O-])=O.[OH2:21]>CS(C)=O>[C:11]([C:10]1[CH:9]=[C:8]([C:1]#[N:2])[C:7]([OH:21])=[CH:20][CH:19]=1)(=[O:12])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O
Reactant: O=C(c1ccccc1)c1ccc([N+](=O)[O-])cc1
Reactant: [C-]#N
Agent: [K+]
Solvent: CS(C)=O
Product: N#Cc1cc(C(=O)c2ccccc2)ccc1O
Temperature: 100 °C

Procedure:
A mixture of dry powdered potassium cyanide (4g.) and 4-nitrobenzophenone (2.27g) was suspended in dimethylsulphoxide (40 ml.) and heated for 4 hours at 100°C. with occasional agitation. The solution was then poured into water and the insoluble neutral fraction removed by filtration. After acidification the filtrate was extracted with ether and the 5-benzoylsalicylonitrile thus obtained was crystallised from aqueous ethanol to give needles, m.p. 185°-186°C.