Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH2:2]([NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].CC(C)=O.[CH3:32][C:33]([CH3:37])([OH:36])[C:34]#[N:35]>N1C=CC=CC=1>[CH2:2]([NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([O:36][C:33]([C:34]#[N:35])([CH3:37])[CH3:32])=[O:24])=[CH:21][CH:20]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)Cl)cc1
Reactant: CC(C)(O)C#N
Agent: Cl
Solvent: c1ccncc1
Solvent: CC(C)=O
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC(C)(C)C#N)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A stirred solution of 20 g. (48.0 m moles) 4-(hexadecylamino)benzoyl chloride hydrochloride in 500 ml. acetone and 50 ml. pyridine is cooled in an ice-water bath, and to this in portions is added 4.3 g. (51 m moles) acetone cyanohydrin. The solution is warmed to room temperature and stirred for an additional two hours. The solvents are evaporated to a yellow gum, which crystallizes to off-white crystals from ethanol.
Reaction SMILES: [CH3:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][C:13]2[N:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[O:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[CH3:29][C:30]([O:33][C:34]([NH:36][C:37]([CH3:42])([C:39](O)=[O:40])[CH3:38])=[O:35])([CH3:32])[CH3:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:42][C:37]([NH:36][C:34](=[O:35])[O:33][C:30]([CH3:32])([CH3:31])[CH3:29])([CH3:38])[C:39]([NH:19][C:16]1[CH:17]=[N:18][C:13]([O:12][C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:11]=2[CH:2]([CH3:1])[CH2:3][CH2:4][O:5]3)=[CH:14][CH:15]=1)=[O:40]
Reactant: CC(C)(C)OC(=O)NC(C)(C)C(=O)O
Reactant: CC1CCOc2cccc(Oc3ccc(N)cn3)c21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC1CCOc2cccc(Oc3ccc(NC(=O)C(C)(C)NC(=O)OC(C)(C)C)cn3)c21
Temperature: 60 °C
Reaction time: 1 h
Yield: 161.1 %

Procedure:
In a 8 mL vial the 6-(4-methylchroman-5-yl)oxypyridin-3-amine (Intermediate 213, 22.9 mg, 0.089 mmol) was dissolved in N,N-Dimethylformamide (3 mL) to give a pale yellow solution. DIPEA (0.069 mL, 0.394 mmol), N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-methylalanine (60.0 mg, 0.295 mmol) and HATU (112 mg, 0.295 mmol) were added. The reaction mixture was shaken at 60° C. for 1 hour. The reaction mixture was evaporated in vacuo and the residue was purified by flash chromatography on silica gel using a column SNAP 25 g and cyclohexane/ethyl acetate from 3:1 to 1:2 as eluents affording the title compound (63.3 mg) as a colorless oil.
Reaction SMILES: [CH2:1]([NH:4][C:5](=O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:2]=[CH2:3].C(Cl)(Cl)=O>CN(C)C=O.O1CCCC1.C1C=CC=CC=1>[CH2:13]([O:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:5]1[NH:4][CH:1]=[CH:2][CH:3]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: C=CCNC(=O)c1ccccc1OCc1ccccc1
Agent: O=C(Cl)Cl
Solvent: c1ccccc1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: c1ccc(COc2ccccc2-c2ccc[nH]2)cc1

Procedure:
2.7 (10 millimoles) of o-benzyloxybenzoic acid allylamide in 20 ml of a 20 per cent strength by weight solution of phosgene in tuluene are stirred, in the presence of 2 drops of dimethylformamide, at room temperature overnight. The residue which remains after distilling off the toluene under reduced pressure at 40° C. bath temperature is taken up in 30 ml of tetrahydrofuran, and the solution is filtered through a pad of glass wool and introduced, in the course of 45 minutes, into an ice-cooled solution of 4.0 g (30 millimoles) of potassium tert.-butylate in 60 ml of a 1:1 (by volume) tetrahydrofuran/benzene mixture, under argon as protective gas. 10 minutes after completion of the addition, the solvent is distilled off under reduced pressure, the residue is partitioned between methylene chloride and water, and the water is extracted twice with methylene chloride.
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1.[I:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1.[O:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35]O)[CH2:30][CH2:29]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[I:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:35][CH2:34][N:31]2[CH2:32][CH2:33][O:28][CH2:29][CH2:30]2)=[CH:23][CH:22]=1
Reactant: OCCN1CCOCC1
Reactant: Oc1ccc(I)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Ic1ccc(OCCN2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 92.4 %

Procedure:
40% DEAD/toluene (2.5 mL) was added to a THF (30 mL) solution of 4-iodophenol (1.0 g), 2-morpholinoethanol (0.72 g) and triphenylphosphine (1.4 g) under ice cooling, and the mixture was stirred for 17 hours at room temperature. After the solvents were distilled off, the resulting residue was purified by NH type silica gel chromatography (gradient elution with hexane/ethyl acetate=90/0→60/40) to obtain 4-[2-(4-iodophenoxy)ethyl]morpholine (colorless oil) (1.4 g, 93%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]#[CH:9].C([Mg]Br)C.Br[CH2:15][C:16]([CH3:27])=[CH:17][CH2:18][CH:19]=[C:20]([CH3:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[Cl-].[NH4+]>CCOCC.O1CCCC1>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]#[C:9][CH2:15][C:16]([CH3:27])=[CH:17][CH2:18][CH:19]=[C:20]([CH3:26])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCC(C)=CCC=C(C)CBr
Reactant: C#CCCCCCCCl
Agent: CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCCCC(C)=CCC=C(C)CC#CCCCCCCCl
Reaction time: 0.33 h

Procedure:
A solution of 12.0 g. of 1-chlorooct-7-yne in 20 ml. of tetrahydrofuran is added to a mixture of 27 ml. of 3N ethyl magnesium bromide in ether and 50 ml. of tetrahydrofuran. The mixture is stirred and heated under reflux for 30 min. under nitrogen, then 0.45 g. of powdered cuprous chloride is added and heating and stirring is continued for 20 min. A solution of 20.0 g. of 1-bromo-2,6-dimethyl-2,5-undecadiene in 15-ml. of tetrahydrofuran is added and the mixture is heated under reflux for 10 hrs., then allowed to stand for about 18 hrs., and poured into saturated aqueous ammonium chloride and ether. The mixture is filtered and the ether solution is separated, washed with water, dried over sodium sulfate, and evaporated to leave a residue comprising 1-chloro-10,14-dimethylnonadeca-10,13-dien-7-yne.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([O:13]C)=[O:12])=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=2)[N:3]=1.[OH-].[Na+]>CO>[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([OH:13])=[O:12])=[C:9]([C:17]([F:19])([F:18])[F:20])[CH:8]=2)[N:3]=1
Reactant: COC(=O)c1ccc(-n2ccc(C)n2)cc1C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1ccn(-c2ccc(C(=O)O)c(C(F)(F)F)c2)n1
Temperature: 25 °C
Yield: 100.8 %

Procedure:
Methyl 4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-benzoate (1.19 g) from Example 93, step b) was dissolved in methanol (10 ml) and a solution of 2.5 N sodium hydroxide (3.3 ml) was added. The reaction was heated at reflux for 90 minutes, cooled to room temperature and concentrated in vacuo to dryness. The residue was partitioned between ethyl acetate and 1 N hydrochloric acid. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to give 1.14 g of the title compound as a colorless solid. MS (FAB) m/z: 271 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:20][CH2:19][C:18]2[C:9](=[N:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17]=2[CH3:21])[CH:8](O)[CH2:7]1)=[O:5])[CH3:2].S(Cl)([Cl:25])=O>>[CH2:1]([O:3][C:4]([N:6]1[CH2:20][CH2:19][C:18]2[C:9](=[N:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17]=2[CH3:21])[CH:8]([Cl:25])[CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCc2c(nc3ccccc3c2C)C(O)C1
Reactant: O=S(Cl)Cl
Product: CCOC(=O)N1CCc2c(nc3ccccc3c2C)C(Cl)C1

Procedure:
1 gm (3.3 millimols) of 5-hydroxy-1,2,4,5-tetrahydro-11methyl-3-azepino[4,5-b]quinoline-carboxylic acid ethyl ester was stirred for 2 hours with 20 ml of thionyl chloride at room temperature. The excess thionyl chloride was then distilled off in vacuo, the residue was dissolved in chloroform, the solution was dried with sodium sulfate, and the solvent was distilled off. After purification of the residue on a silicagel column with benzene/ethyl acetate (8:2) as the eluant, the yield was 0.55 gm (52% of theory), m.p. 131° C.
Reaction SMILES: N[C@H:2]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[C:3]([OH:5])=[O:4].[BrH:12].N([O-])=O.[Na+]>O>[Br:12][C@H:2]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[C:3]([OH:5])=[O:4]
Reactant: Br
Reactant: N[C@@H](C(=O)O)C1CCCCC1
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=C(O)[C@H](Br)C1CCCCC1
Reaction time: 2 h
Yield: 92.5 %

Procedure:
The (R)-2-amino-2-cyclohexylacetic acid (H-Cyclohexyl-D-Gly-OH, 1 g, 6.36 mmol), which is commercially available from Bachem California Inc., Torrance, Calif. 90505, was dissolved in a mixture of HBr 48% (5.8 niL, 50.9 mmol) and H2O (20 mL). At 0° C., a solution of NaNO2 (1.4 g, 20.4 mmol) in H2O (10 mL) was added over a period of 30 min. The reaction was stirred for two hours. The reaction mixture was degassed in vacuo and extracted with EtOAc (2×2mL). The extracts were washed with water (15 mL), dried (Na2SO4), filtered and evaporated to give 1.3 g (92% yield) of the (R)-2-bromo-2-cyclohexylacetic acid as a white solid.
Reaction SMILES: C([C:3]1(C#C)[C:12]([CH3:14])([CH3:13])[C:11]2[C:6](=[C:7]([Si](C)(C)C)[CH:8]=[C:9]([C:15]([O-:17])=[O:16])[CH:10]=2)[O:5][C:4]1([CH3:23])[CH3:22])C.[OH-].[Na+].Cl.[CH2:29](O)[CH3:30]>>[C:29]([C:7]1[CH:8]=[C:9]([C:15]([OH:17])=[O:16])[CH:10]=[C:11]2[C:6]=1[O:5][C:4]([CH3:22])([CH3:23])[CH2:3][C:12]2([CH3:13])[CH3:14])#[CH:30]
Reactant: C#CC1(CC)C(C)(C)Oc2c(cc(C(=O)[O-])cc2[Si](C)(C)C)C1(C)C
Reactant: CCO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: C#Cc1cc(C(=O)O)cc2c1OC(C)(C)CC2(C)C
Yield: 84 %

Procedure:
A solution of ethyl-8-trimethylsilanyl-ethynyl-2,2,4,4-tetramethylchroman-6-carboxylate (Compound 25, 0.525 g, 1.47 mmol) in ethanol (5 mL) was treated with 2N aqueous sodium hydroxide solution (5 mL, 10 mmol) and the resulting solution was adjusted to pH˜5 with 10% aqueous hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a brown solid (0.316 g, 84%).
Reaction SMILES: F[C:2]1[CH:3]=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[CH3:23][C:24]1([CH3:30])[CH2:29][CH2:28][CH2:27][CH2:26][NH:25]1.CCN(C(C)C)C(C)C>>[CH3:23][C:24]1([CH3:30])[CH2:29][CH2:28][CH2:27][CH2:26][N:25]1[C:2]1[CH:3]=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2
Reactant: CC1(C)CCCCN1
Reactant: O=C1NCCc2[nH]c(-c3cccc4ncc(F)nc34)cc21
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: CC1(C)CCCCN1c1cnc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
Temperature: 120 °C
Yield: 14 %

Procedure:
Prepared similarly to that described in Example 210 using 2-(3-fluoroquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 210i; 110 mg, 0.390 mmol), 2,2-dimethylpiperidine hydrochloride (117 mg, 0.779 mmol, Anichem, North Brunswick, N.J.), and DIPEA (339 μl, 1.948 mmol), heating at 120° C. for 5 h. Purification by rpHPLC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% ACN/water with 0.1% TFA) provided 2-(3-(2,2-dimethylpiperidin-1-yl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (14% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48 (s, 6H) 1.61-1.82 (m, 6H) 2.87 (t, J=6.85 Hz, 2H) 3.45 (td, J=6.80, 2.45 Hz, 2H) 3.61-3.66 (m, 2H) 6.96 (br. s., 1H) 7.09 (d, J=2.35 Hz, 1H) 7.52 (t, J=7.82 Hz, 1H) 7.73 (dd, J=8.12, 1.27 Hz, 1H) 7.93 (dd, J=7.43, 1.37 Hz, 1H) 8.78 (s, 1H) 11.76 (br. s., 1H). MS (ESI, pos. ion) m/z: 376.3 (M+1).
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[N:11]([NH:12][C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[C:10](=[O:21])[NH:9][C:8](=[O:22])[CH:7]=1.[H+].[B-](F)(F)(F)[F:25]>O>[F:25][C:6]1[N:11]([NH:12][C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[C:10](=[O:21])[NH:9][C:8](=[O:22])[CH:7]=1
Reactant: Cc1cccc(C)c1Nn1c(N)cc(=O)[nH]c1=O
Reactant: F[B-](F)(F)F
Agent: O=N[O-]
Agent: [H+]
Agent: [Na+]
Solvent: O
Product: Cc1cccc(C)c1Nn1c(F)cc(=O)[nH]c1=O

Procedure:
Sodium nitrite (1.1 mole) dissolved in water is slowly added to a cool (0°-5°) solution of 6-amino-1-(2,6-dimethylanilino)-2,4-pyrimidinedione (1 mole) in dilute fluoboric acid. The precipitate which forms is filtered off, washed with water, dried and pyrolyzed under nitrogen (only a small amount at a time) to give 6-fluoro-1-(2,6-dimethylanilino)-2,4-pyrimidinedione.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]#[C:10][CH3:11]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]#[C:10][C:11]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: CC#Cc1ccccc1OC
Solvent: Cc1ccccc1
Product: COc1ccccc1C#Cc1ccccc1OC
Temperature: 55 °C
Reaction time: 2 h
Yield: 97.4 %

Procedure:
In a dry 25 mL Schlenk-tube, which has been flooded with argon, complex 24b (58 mg, 0.05 mmol, 5 mol %) and MnCl2 (6.3 mg, 0.05 mmol) were dissolved in 1 mL of toluene. Subsequently, the mixture was heated for 30 to 80° C. and was re-cooled to room temperature. The solution of the catalyst was transferred into a suspension of 1-methoxy-2-(prop-1-inyl)benzene (325 mg, 1 mmol) and molecular sieve (1 g, 5 Å, powder) in 4 mL of toluene and the reaction mixture was stirred for 2 h at room temperature. Subsequently, it was filtered over a short silica gel column (2 cm), the filtrate was concentrated and the residue was purified by means of column chromatography (SiO2, hexane/EtOAc, 20:1). One obtains 1,2-bis(2-methoxyphenyl)ethine (116 mg, 97%) as colorless solid. M.p.=126-127° C.; 1H NMR (400 MHz, CD2Cl2): δ=7.49 (ddd, J=7.3, 1.6, 0.5 Hz, 2H), 7.33 (ddd, J=7.9, 7.7, 1.9 Hz, 2H), 6.95 (td, J=7.9, 1.0 Hz, 4H), 3.92 (s, 6H); 13C NMR (100 MHz, CD2Cl2): δ=160.3 (2×C), 133.7 (2×CH), 130.1 (2×CH), 120.8 (2×CH), 113.0 (2×C), 111.3 (2×CH), 90.1 (2×C), 56.2 (2×CH3); IR (film): v=3105, 3033, 2998, 2963, 2937, 2833, 1945, 1903, 1863, 1598, 1574, 1498, 1464, 1456, 1432, 1274, 1241, 1184, 1162, 1115, 1047, 1020, 937, 750 cm−1; MS (EI) m/z (%): 238 [M+] (100), 237 (32), 223 (23), 221 (15), 207 (10), 195 (5), 178 (8), 165 (14), 152 (9), 131 (19), 111 (6), 97 (3), 89 (3); HRMS (ESI): m/z: calculated for C16H14O2+Na: 261.0886. found: 261.0884.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([C:7]([O:9][CH3:10])=[O:8])=[CH:3][CH:2]=1.[C:12]1(O)[CH:17]=[CH:16]C=[CH:14][CH:13]=1>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([C:7]([O:9][C:10]2[CH:16]=[CH:17][CH:12]=[CH:13][CH:14]=2)=[O:8])=[CH:5][CH:6]=1
Reactant: Oc1ccccc1
Reactant: COC(=O)c1ccc(C)cc1
Agent: [Ti+4]
Agent: CC(C)[O-]
Product: Cc1ccc(C(=O)Oc2ccccc2)cc1
Temperature: 190 °C
Reaction time: 6 h

Procedure:
A thermometer and Claisen head were attached to a three-necked flask having an internal volume of 500 ml. A receiver having a gage was attached to the Claisen head via a condenser to make a distillation apparatus. Into this apparatus were charged methyl p-toluate 75 g (0.50 mole), phenol 376 g (4.0 mole) and titanium tetraisopropoxide 1.42 g (5.0 mmole). The contents were reacted with stirring in a 190° C. bath. The reaction was conducted at atmospheric pressure for six hours while removing methanol produced in the reaction. Then, the temperature of the bath was elevated to 196° to 198° C., and phenol was removed by distillation in an amount of as much as 150 g. The remaining phenol and methyl p-toluate were removed by distilling under vacuum (85 mmHg). Then, the vacuum pressure was decreased to obtain phenyl p-toluate. The boiling point was 183° to 185° C./18 mmHg, and the product was a slightly yellow colored white solid. The yield was 72.98 g, (69% in terms of methyl p-toluate). The melting point was 74° to 76° C.
Reaction SMILES: [Mg].BrCCBr.[CH3:6][N:7]([CH3:12])[CH2:8][CH2:9][CH2:10]Cl.[Br:13][C:14]1[CH:15]=[CH:16][C:17]2[O:27][C:20]3([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:19](=[O:28])[C:18]=2[CH:29]=1.[Cl-].[NH4+]>C(OCC)C.C1C=CC=CC=1>[Br:13][C:14]1[CH:15]=[CH:16][C:17]2[O:27][C:20]3([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:19]([CH2:10][CH2:9][CH2:8][N:7]([CH3:12])[CH3:6])([OH:28])[C:18]=2[CH:29]=1
Reactant: O=C1c2cc(Br)ccc2OC12CCCCCC2
Reactant: CN(C)CCCCl
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Solvent: c1ccccc1
Solvent: BrCCBr
Product: CN(C)CCCC1(O)c2cc(Br)ccc2OC12CCCCCC2
Temperature: 0 °C

Procedure:
A stirred mixture of 2.72 g of magnesium turnings in 32 ml of diethyl ether containing about 0.5 ml of 1,2-dibromoethane was treated with a solution of 13.62 g of freshly distilled 3-dimethylaminopropyl chloride in 32 ml of ether at a rate sufficient to produce and maintain reflux. After the addition, a solution of 16.53 g of 5-bromo-spiro[benzofuran-2(3H),1'-cycloheptan]-3-one in 65 ml of benzene was added, followed by an additional 32 ml of ether and the mixture was refluxed overnight under nitrogen. After 14.5 hours of reflux, the mixture was cooled in ice water and treated cautiously with 140 ml of saturated aqueous ammonium chloride solution. The mixture was then poured into a separatory funnel, the flask was rinsed with a few hundred ml's of distilled water, and the combined mixture was extracted with ether (2×400 ml). The combined organic extracts were washed with water (250 ml) and saturated sodium chloride solution (250 ml), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to an oil which crystallized to a solid. This material was triturated with petroleum ether and filtered to afford 8.74 g of crude product. Preparative HPLC purification of this material was performed using two columns and 5% methanol/dichloromethane as a solvent. The purest fractions containing the desired material were combined and concentrated in vacuo to a solid. This material was triturated with hexane, filtered and dried to afford 4.16 g of a solid, m.p. 126°-128° C.
Reaction SMILES: [N:1]([O-])=O.[Na+].[C:5]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([NH2:17])=[CH:9][CH:8]=1)#[N:6]>O.Cl>[C:5]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([NH:17][NH2:1])=[CH:9][CH:8]=1)#[N:6]
Reactant: N#Cc1ccc(N)c2ccccc12
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: N#Cc1ccc(NN)c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of 4.09 g of sodium nitrite in 30 ml of water is added to a solution, cooled to 0° C., of 8.35 g of 4-cyano-1-naphthylamine in 180 ml of 1N HCl. The mixture is left stirring for 1 hour 15 minutes at 0° C. It is cooled to -10° C., and a solution of 41.75 g of stannous chloride dihydrate in 42 ml of concentrated HCl is added slowly. The reaction mixture is stirred for 1 hour, allowing the temperature to rise to RT. It is filtered. The residue is suspended in water and 20 ml of concentrated NaOH are added. The expected product is obtained after filtration, rinses with water and then drying under vacuum, m=8.6 g.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][Si](C(C)(C)C)(C)C)[C:3]=1[C:4]#[N:5].[S:23](Cl)(=[O:26])(=[O:25])[NH2:24]>O>[S:23](=[O:26])(=[O:25])([O:15][CH2:14][CH2:13][CH2:12][CH2:11][O:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([NH:1][S:23](=[O:26])(=[O:25])[NH2:24])[C:3]=1[C:4]#[N:5])[NH2:24]
Reactant: CC(C)(C)[Si](C)(C)OCCCCOc1cccc(N)c1C#N
Reactant: NS(=O)(=O)Cl
Solvent: O
Product: N#Cc1c(NS(N)(=O)=O)cccc1OCCCCOS(N)(=O)=O
Yield: 63 %

Procedure:
Prepared as in Example 215a from 2-amino-6-(4-(tert-butyldimethylsilyloxy)butoxy)benzonitrile (Example 235b) and sulfamoyl chloride in 63% yield. MS 382 (M++H2O).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[NH:11][C:12]([CH2:14][CH2:15][CH3:16])=O)[NH:7][C:6](=[O:17])[C:5]2([CH3:19])[CH3:18].C(O)(=O)CCC>>[CH2:14]([C:12]1[NH:11][C:10]2[CH:9]=[C:8]3[NH:7][C:6](=[O:17])[C:5]([CH3:19])([CH3:18])[C:4]3=[CH:3][C:2]=2[N:1]=1)[CH2:15][CH3:16]
Reactant: CCCC(=O)Nc1cc2c(cc1N)C(C)(C)C(=O)N2
Solvent: CCCC(=O)O
Product: CCCc1nc2cc3c(cc2[nH]1)NC(=O)C3(C)C

Procedure:
According to the process of Example 5, from 0.7 g. (2.7 mmole) 5-amino-6-n-propylcarbonylamino-3,3-dimethylindolin-2-one and 7 ml. butyric acid, after 1 hour at 100° C., there is obtained 0.4 g. (61% of theory) of the title compound; m.p. 284°-285° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:18]=[CH:17][C:16]2[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[C:19]3[O:20][C:21]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:22][C:23](=[O:25])[CH:24]=3)[S:8][C:7]=2[CH:6]=1)=[O:4].[OH-].[Na+:33]>CO>[Na+:33].[N:26]1([C:21]2[O:20][C:19]([C:13]3[CH:12]=[CH:11][CH:10]=[C:9]4[C:14]=3[S:15][C:16]3[CH:17]=[CH:18][C:5]([C:3]([O-:4])=[O:2])=[CH:6][C:7]=3[S:8]4)=[CH:24][C:23](=[O:25])[CH:22]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1
Reactant: COC(=O)c1ccc2c(c1)Sc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C([O-])c1ccc2c(c1)Sc1cccc(-c3cc(=O)cc(N4CCOCC4)o3)c1S2
Temperature: 80 °C

Procedure:
6-(6-Morpholin-4-yl-4-oxo-4H-pyran-2-yl)-thianthrene-2-carboxylic acid methyl ester (1.1 g, 2.43 mmol) and NaOH Pellets (97 mg, 2.43 mmol) were dissolved in methanol (40 ml). The brown suspension was heated to 80° C. under N2 for 24 hours. The solvent was removed in vacuo and the residue was triturated with diethyl ether. The product was collected by filtration as a fine dark brown powder (1.11 g, 99%). m/z (LC-MS, ESP), RT=3.90 min, (M−−1)=438
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[CH2:12]([C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][CH:16]=1)[CH2:13][CH3:14].C(N(CC)CC)C>C1COCC1>[O:11]=[C:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][C:19](=[O:20])[C:18]3[CH:22]=[CH:23][C:15]([CH2:12][CH2:13][CH3:14])=[CH:16][CH:17]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:6]1
Reactant: Nc1ccc2c(c1)CCC2=O
Reactant: CCCc1ccc(C(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCc1ccc(C(=O)Nc2ccc3c(c2)CCC3=O)cc1
Yield: 64 %

Procedure:
Reaction of 5-amino-indan-1-one (75 mg, 0.50 mmol) in THF (6 mL) with 4-propylbenzoyl chloride (108 μL, 0.65 mmol) in presence of triethylamine (90 μL, 0.65 mmol) according to method A gave N-(1-oxo-indan-5-yl)-4-propyl-benzamide (94 mg, 0.32 mmol, 64% yield) as a white powder after purification on silica gel (eluent EtOAc/DCM 0/10 to 1/9).
Reaction SMILES: [NH2:1][O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[N:13]=[C:14]([NH:17][C:18](=[O:20])[CH3:19])[S:15][CH:16]=2)=[CH:6][CH:5]=1.[CH2:21]=O>CO>[CH2:21]=[N:1][O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[N:13]=[C:14]([NH:17][C:18](=[O:20])[CH3:19])[S:15][CH:16]=2)=[CH:6][CH:5]=1
Reactant: CC(=O)Nc1nc(CCc2ccc(CON)cc2)cs1
Reactant: C=O
Solvent: CO
Product: C=NOCc1ccc(CCc2csc(NC(C)=O)n2)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
N-[4-(2-{4-[(Aminooxy)methyl]phenyl}ethyl)-1,3-thiazol-2-yl]acetamide (30 mg) prepared in a similar manner according to Production Example 16, 37% formaldehyde (8 μl) and dry methanol (1 ml) were combined under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 6 hours and concentrated in vacuo. The residue was purified by preparative silica gel column chromatography with chloroform/methanol (20:1) as an eluent, and triturated with ethyl ether to give N-{4-[2-(4-{[(methyleneamino)oxy]methyl}-phenyl)ethyl]-1,3-thiazol-2-yl}acetamide (20.9 mg) as a colorless solid.