Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH3:17].[NH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][CH3:17]
Reactant: C1CCNCC1
Reactant: COCCCCOc1cc(C)ccc1C(=O)OC
Product: COCCCCOc1cc(CN2CCCCC2)ccc1C(=O)OC

Procedure:
The 2-(4-methoxybutoxy)-4-(piperidin-1-ylmethyl)-benzoic acid methyl ester that is used is prepared in a manner analogous to that described in Example 30 An) from 2-(4-methoxybutoxy)-4-methyl-benzoic acid methyl ester and piperidine, with subsequent purification of the crude product by FC (eluants C and M): brown oil, Rf (N)=0.34.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([Sn](C)(C)C)=[CH:14][CH:13]=1.O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8](=[O:10])[CH3:9])=[CH:14][CH:13]=1
Reactant: Cc1ccc([Sn](C)(C)C)cc1
Reactant: CC(=O)c1ccccc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1ccccc1-c1ccc(C)cc1
Temperature: 150 °C
Yield: 71.2 %

Procedure:
A vigorously stirred solution of 13.25 g (66 mmol) of 2'-bromoacetophenone and 22.8 g (89 mmol) of 4-methylphenyltrimethylstannane in 190 mL of dimethylformamide under a nitrogen atmosphere was treated with 8.64 g (12 mmol) of bis(triphenylphosphine)palladium(II) chloride and the resulting mixture heated at 150° C. for 6 hours. The reaction mixture was cooled, poured into water (1000 mL) and the resultant suspension extracted with ethyl ether. The combined extracts were washed with water (4×), dried over magnesium sulfate and evaporated under vacuum. The residue was purified by preparative high pressure liquid chromatography on silica gel, eluting with hexane/ethyl acetate (10:1) to give 9.8 g (47 mmol, 71%) of product as an oil. EI-MS: calculated for C15H14O 210: found 210 (M+). 1H NMR (200 MHz, CDCl3): δ 1.98 (s, 3H), 2.37 (s, 3H), 7.20 (s, 4H), 7.3-7.5 (m, 4H).
Reaction SMILES: [N:1]1([C:6]2[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[P:12]([O-:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15]>>[N:1]1([C:6]2([P:12]([O:16][CH2:17][CH3:18])(=[O:19])[O:13][CH2:14][CH3:15])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CCOP([O-])OCC
Reactant: C1=C(N2CCCC2)CCCC1
Product: CCOP(=O)(OCC)C1(N2CCCC2)CCCCC1

Procedure:
A mixture of 1-pyrrolidinocyclohexene (15.1 g; 0.1 mole) and diethyl phosphite (13.8 g; 0.1 mole) was heated for 2 hours on a steam bath. The resulting liquid showed no absorption in the infrared for C=C or P-H. Distillation yielded pure diethyl 1-pyrrolidinocyclohexane-1-phosphonate, bp 80°-85°/0.1 mm. ##STR8##
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].[C:11]1([O:17][CH3:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Al+3].[Cl-].[Cl-].[Cl-].Cl>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:5]([C:14]2[CH:15]=[CH:16][C:11]([O:17][CH3:18])=[CH:12][CH:13]=2)=[O:6])[CH:8]=[CH:9][CH:10]=1
Reactant: COc1ccccc1
Reactant: O=C(Cl)c1cccc(Br)c1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(C(=O)c2cccc(Br)c2)cc1
Yield: 79.6 %

Procedure:
To a cooled (0° C.) mixture of 3-bromobenzoyl chloride (5-a, 178 g, 0.82 mol) and anisole (110 g, 1.03 mol) in DCM (2.0 L) was added AlCl3 (138 g, 1.03 mol) portion wise with stirring under N2. The resulting reaction mixture was allowed to stir at r.t overnight. The reaction mixture was poured into 20% HCl (1500 ml), stirred for 1 h, and layers were separated. The aqueous layer was further extracted with DCM (2×750 ml). The combined organic layer was washed with water, brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was washed with hexane to afford the product, 5-b, (190 g, 84%).
Reaction SMILES: C([O:5][C:6]([C@@H:8]1[CH2:12][C@H:11]([N:13]([CH3:15])[CH3:14])[CH2:10][NH:9]1)=O)CCC.[NH3:16]>CO>[CH3:14][N:13]([CH3:15])[C@@H:11]1[CH2:10][NH:9][C@H:8]([C:6]([NH2:16])=[O:5])[CH2:12]1
Reactant: CCCCOC(=O)[C@@H]1C[C@H](N(C)C)CN1
Reactant: N
Solvent: CO
Product: CN(C)[C@@H]1CN[C@H](C(N)=O)C1

Procedure:
A solution of (2S,4S)-4-Dimethylamino-pyrrolidine-2-carboxylic acid butyl ester (326 mg) and 7M ammonia in methanol (8 ml) is stood for 18 hours at room temperature in a sealed vessel. Filtration, evaporation and trituration with diethyl ether/methanol gives the title compound as a beige solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:38]=[CH:37][C:12]([O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][C:15]=2[NH:23][C:24]2[C:25]3[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[N:30][C:26]=3[N:27]=[CH:28][N:29]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:39][O:40][C:41]1[CH:42]=[C:43]([NH2:47])[CH:44]=[CH:45][CH:46]=1>>[CH2:1]([O:8][C:9]1[CH:38]=[CH:37][C:12]([O:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:47][C:43]3[CH:44]=[CH:45][CH:46]=[C:41]([O:40][CH3:39])[CH:42]=3)=[O:19])=[CH:16][C:15]=2[NH:23][C:24]2[C:25]3[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[N:30][C:26]=3[N:27]=[CH:28][N:29]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cccc(N)c1
Reactant: CC(C)c1ccc2c(Nc3cc(C(=O)Cl)ccc3Oc3ccc(OCc4ccccc4)cc3)ncnc2n1
Product: COc1cccc(NC(=O)c2ccc(Oc3ccc(OCc4ccccc4)cc3)c(Nc3ncnc4nc(C(C)C)ccc34)c2)c1

Procedure:
A solution of the product from Example 43D and 3-Methoxy-phenylamine was reacted to provide 4-(4-Benzyloxy-phenoxy)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-N-(3-methoxy-phenyl)-benzamide using the procedure from Example 43E. The material was then deprotected using the procedure from Example 43F to provide the crude title compound which was purified by column chromatography on silica gel using methanol/dichloromethane as eluent to provide the title product (12 mg, 40%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.32 (d, J=6.99 Hz, 6 H) 3.11-3.29 (m, 1 H) 3.75 (s, 3 H) 6.68 (dd, J=8.09, 1.84 Hz, 1 H) 6.75 (d, J=8.82 Hz, 2 H) 6.89 (t, J=8.64 Hz, 3 H) 7.24 (t, J=8.09 Hz, 1 H) 7.37 (d, J=8.09 Hz, 1 H) 7.45 (t, J=2.21 Hz, 1 H) 7.60 (d, J=8.46 Hz, 1 H) 7.86 (dd, J=8.64, 1.65 Hz, 1 H) 8.17 (s, 1 H) 8.61 (s, 1 H) 8.82 (d, J=8.46 Hz, 1 H) 9.38 (s, 1 H) 10.01 (s, 1 H) 10.15 (s, 1 H); MS (ESI+) m/z 522 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:20][CH2:19][CH2:18]2)[N:3]=1.O.[NH2:22][NH2:23]>CO>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:22][NH:23]3)=[CH:14][CH:15]=2)[CH:5]=[C:4]([N:17]2[CH2:20][CH2:19][CH2:18]2)[N:3]=1
Reactant: N#Cc1ccc(-c2cc(N3CCC3)nc(N)n2)cc1F
Reactant: NN
Solvent: O
Solvent: CO
Product: Nc1nc(-c2ccc3c(N)n[nH]c3c2)cc(N2CCC2)n1
Temperature: 95 °C
Reaction time: 8 h
Yield: 44.5 %

Procedure:
In a 25 mL sealable tube were combined 4-[2-amino-6-(1-azetidinyl)-4-pyrimidinyl]-2-fluorobenzonitrile (0.21 g, 0.79 mmol), hydrazine monohydrate (0.77 mL, 15.8 mmol) and CH3OH (10 mL). The vial was sealed, and the reaction mixture was stirred overnight at 95° C. The reaction was concentrated, and the resulting yellow solid was diluted with EtOH (2 mL) and water (5 mL). The mixture was sonicated, and the solid was filtered, washed with water, and dried under vacuum to afford the title compound (99 mg, 43%) as a light yellow solid. LC-MS (ES) m/z=282 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 2.33 (m, 2H), 4.02 (m, 4H), 5.38 (s, 2H), 6.13 (bs, 2H), 6.14 (s, 1H), 7.51 (dd, J=8.3, 1.3 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.91 (s, 1H), 11.50 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11](N3CCC4C=CNC=4C3C)=[O:12])[CH:10]=2)[CH:7]=1.[CH3:23][O:24][C:25]1[O:26][C:27]2[CH2:32][CH2:31][NH:30][CH:29]([CH3:33])[C:28]=2[N:34]=1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:30]3[CH2:31][CH2:32][C:27]4[O:26][C:25]([O:24][CH3:23])=[N:34][C:28]=4[CH:29]3[CH3:33])=[O:12])[CH:10]=2)[CH:7]=1
Reactant: CC1c2[nH]ccc2CCN1C(=O)c1cc2ncc(Br)cn2n1
Reactant: COc1nc2c(o1)CCNC2C
Product: COc1nc2c(o1)CCN(C(=O)c1cc3ncc(Br)cn3n1)C2C

Procedure:
(6-Bromo-pyrazolo[1,5-a]pyrimidin-2-yl)-(7-methyl-1,4,5,7-tetrahydro-pyrrolo[2,3-c]pyridin-6-yl)-methanone is reacted with 2-methoxy-4-methyl-4,5,6,7-tetrahydrooxazolo[4,5-c]pyridine to provide the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:16][CH:17]([CH3:19])[CH3:18])C(C=CC(O)=O)=O)=[C:4]([CH:20]([OH:35])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[O:27][CH2:28][C:29]2C=CC=CC=2)[CH:3]=1>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:16][CH:17]([CH3:18])[CH3:19])=[C:4]([CH:3]=1)[CH:20]([OH:35])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[O:27][CH2:28][CH3:29]
Reactant: CC(C)CN(C(=O)C=CC(=O)O)c1ccc(Cl)cc1C(O)c1ccccc1OCc1ccccc1
Solvent: CCO
Product: CCOc1ccccc1C(O)c1cc(Cl)ccc1NCC(C)C

Procedure:
In 150 ml of ethanol was dissolved 6.0 g of ethyl ester of 3-[N-[4-chloro-2-[2-benzyloxy-α-hydroxybenzyl]phenyl]-N-isobutylcarbamoyl]acrylic acid, as obtained in (4), to which was added 3.18 g of potassium carbonate; the mixture was then stirred overnight. The solvent was distilled off under reduced pressure, and the residue was subjected to extraction with 150 ml of water and 200 ml of ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate, then distilled off under reduced pressure. The residue was purified by means of silica gel column chromatography (eluent, hexane:ethyl acetate=5:1) to yield 5.8 g of ethyl ester of trans-5-(2-benzyloxyphenyl)-7-chloro-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid as prism crystals, m.p. 146° to 147° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:10]([OH:20])[CH2:11][CH2:12][NH:13][C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:21]([C:23]([OH:30])([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])#[CH:22]>>[F:16][C:15]([F:18])([F:17])[C:14]([NH:13][CH2:12][CH2:11][CH:10]([OH:20])[C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([C:22]#[C:21][C:23]([OH:30])([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])[CH:3]=1)=[O:19]
Reactant: COc1ccc(C(O)CCNC(=O)C(F)(F)F)cc1Br
Reactant: C#CC(O)(CCC)CCC
Product: CCCC(O)(C#Cc1cc(C(O)CCNC(=O)C(F)(F)F)ccc1OC)CCC

Procedure:
N-(3-(3-bromo-4-methoxyphenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide was coupled with 4-ethynylheptan-4-ol to give 2,2,2-trifluoro-N-(3-hydroxy-3-(3-(3-hydroxy-3-propylhex-1-ynyl)-4-methoxyphenyl)propyl)acetamide as a yellow oil. Yield (0.92 g, 55%): 1H NMR (400 MHz, DMSO-d6) δ 9.31 (t, J=5.0 Hz, 1H), 7.24-7.21 (m, 2H), 6.95 (d, J=9.2 Hz, 1H), 5.25 (d, J=4.8 Hz, 1H), 5.05 (s, 1H), 4.51-4.47 (m, 1H), 3.75 (s, 3H), 3.24-3.17 (m, 2H), 1.77-1.72 (m, 2H), 1.61-1.42 (m, 8H), 0.89 (t, J=7.0 Hz, 6H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][S:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=2)[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(O)(=O)C.[Fe]>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:8][S:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1
Reactant: O=[N+]([O-])c1ccc(SCc2cccc(F)c2)cc1
Agent: [Fe]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Nc1ccc(SCc2cccc(F)c2)cc1

Procedure:
1.75 g (6.7 mmol) 1-Fluoro-3-(4-nitrophenylsulfanylmethyl)-benzene and 5.55 g (100 mmol) of iron-powder are suspended in 35 ml water and 0.2 ml acetic acid. The mixture is heated overnight at 90°, then cooled and treated with saturated sodium carbonate solution. The suspension is filtered, the solid washed several times with ethyl acetate and the aqueous phase extracted 3 times with ethyl acetate. The combined organic phases are dried and evaporated to give 1.18 g (76%) of a yellowish waxy solid. MS: m/e=234.3 (M++H).
Reaction SMILES: [C:1]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:13])[CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].Br[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]Br.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[C:2]1([C:1]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])([C:3]([O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:4])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: O=C(CC(=O)OCc1ccccc1)OCc1ccccc1
Reactant: BrCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: O=C(OCc1ccccc1)C1(C(=O)OCc2ccccc2)CCCCC1

Procedure:
A solution of dibenzyl malonate (40 g, 161 mmol), 1,5-dibromopentane (22 mL, 161 mmol) and potassium carbonate (56 g, 402 mmol) in 300 mL of DMSO was stirred for 48 h in an oil bath at 50° C. The mixture was diluted with water and extracted with ethyl acetate (2×). The combined organic portions were dried over magnesium sulfate and concentrated. Flash chromatography (400 g silica, 15/1 hexane/EtOAc) gave the desired product. 1H NMR (500 MHz, CDCl3) δ1.4-1.5 (m, 1H), 1.52-1.6 (m, 5H), 2.03-2.1 (m, 4H), 5.13 (s, 4H), 7.22-7.38 (m, 10H).
Reaction SMILES: [BH4-].[Na+].[O:3]=[C:4]([CH3:25])[C:5]([C:8]1[CH:9]=[C:10]([C:20]([CH3:24])([CH3:23])[C:21]#[N:22])[CH:11]=[C:12]([CH2:14][N:15]2[CH:19]=[N:18][CH:17]=[N:16]2)[CH:13]=1)([CH3:7])[CH3:6]>C(O)C.O>[OH:3][CH:4]([CH3:25])[C:5]([C:8]1[CH:9]=[C:10]([C:20]([CH3:24])([CH3:23])[C:21]#[N:22])[CH:11]=[C:12]([CH2:14][N:15]2[CH:19]=[N:18][CH:17]=[N:16]2)[CH:13]=1)([CH3:7])[CH3:6]
Reactant: CC(=O)C(C)(C)c1cc(Cn2cncn2)cc(C(C)(C)C#N)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(O)C(C)(C)c1cc(Cn2cncn2)cc(C(C)(C)C#N)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Sodium borohydride (20 mg) was added to a solution of 2-[3-(2-oxo-1,1-dimethylpropyl)-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropiononitrile (prepared as described in Example 2--40 mg) in ethanol (2 ml) and the mixture was stirred at room temperature for 18 h. The mixture was diluted with water and extracted with ethyl acetate, and the extract was dried and evaporated to dryness under reduced pressure. The residue was purified by flash chromatography, using methanol (1% by volume) in ethyl acetate as eluant, to give 2-[3-(2-hydroxy-1,1-dimethylpropyl)-5-(1H-1,2,4-triazol-1-yl-methyl)phenyl]-2-methylpropiononitrile, mp 83°-84°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:15]1([CH2:21]Br)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C=O.O>[C:15]1([CH2:21][O:8][C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][CH:5]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Oc1cccc(Br)c1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Brc1cccc(OCc2ccccc2)c1
Temperature: 80 °C
Reaction time: 1 h
Yield: 89.5 %

Procedure:
Under a nitrogen atmosphere, a solution of 50.0 grams (0.29 mole) of 3-bromophenol and 120.0 grams (0.87 mole) of potassium carbonate in 400 mL of N,N-dimethylformamide was stirred, and heated to 80° C. To this was added portionwise, 36.1 mL (0.30 mole) of phenylmethyl bromide during a 20 minute period. Upon completion of addition, the reaction mixture was stirred at 80° C. during a one hour period. After this time, the reaction mixture was allowed to cool to ambient temperature, where it was diluted with 600 mL of water. The mixture was extracted with 600 mL of diethyl ether. The extract was then washed with three 50 mL portions of water, and then it was concentrated under reduced pressure to a residual solid. The solid was recrystallized with 250 mL of methanol, yielding 68.3 grams of 3-(phenylmethoxy)phenyl bromide. The. NMR spectrum was consistent with the proposed structure.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:14]([OH:15])=[C:13]2[C:8]([CH:9]=[CH:10][CH:11]=[N:12]2)=[CH:7][CH:6]=1)=O.[NH3:16]>>[OH:15][C:14]1[C:5]([C:3]([NH2:16])=[O:2])=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[CH:9]2
Reactant: N
Reactant: COC(=O)c1ccc2cccnc2c1O
Product: NC(=O)c1ccc2cccnc2c1O

Procedure:
8-Hydroxy-7-quinolinecarboxylic acid methyl ester [as reported by Eckstein, Z. et al. in Pol. J. Chem. 1979, 53(11), 2373-7 (C.A. 92, 215243s)] is reacted with excess ammonia in a steel bomb for 12-18 hr. The excess ammonia is allowed to evaporate and the residue is crystallized from a suitable solvent to give the title compound.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][Si:5]([CH3:12])([O:9][CH2:10][CH3:11])[O:6][CH2:7][CH3:8].[NH3:13]>>[NH2:13][CH2:2][CH2:3][CH2:4][Si:5]([CH3:12])([O:9][CH2:10][CH3:11])[O:6][CH2:7][CH3:8]
Reactant: CCO[Si](C)(CCCCl)OCC
Reactant: N
Product: CCO[Si](C)(CCCN)OCC

Procedure:
According to Example 1, 6.6 kg (31.1 mol) 3-chloropropylmethyldiethoxysilane are reacted with 24 kg (1412 mol) ammonia, excess ammonia is removed by pressure distillation and flash processes and the 3-aminopropylmethyldiethoxysilane that is formed is isolated by filtration and vacuum distillation.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[C:31]([O:32][CH3:33])=[C:30]([O:34][CH3:35])[CH:29]=[CH:28][C:23]=1[CH:24]=[CH:25][CH2:26]Br>>[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:19][CH2:18][N:17]([CH2:26][CH:25]=[CH:24][C:23]3[CH:28]=[CH:29][C:30]([O:34][CH3:35])=[C:31]([O:32][CH3:33])[C:22]=3[O:21][CH3:20])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C=CCBr)c(OC)c1OC
Reactant: c1ccc(Oc2ccc(C3CCNCC3)cc2)cc1
Product: COc1ccc(C=CCN2CCC(c3ccc(Oc4ccccc4)cc3)CC2)c(OC)c1OC

Procedure:
The same procedure was followed as in Example 11 using the compound (9) synthesized in Example 2 and (2,3,4-trimethoxy)cinnamyl bromide to produce the above.
Reaction SMILES: [CH3:1][N:2]([CH3:14])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][C:12]=1[I:13])[NH2:9].[Cl:15][C:16]1[CH:29]=[CH:28][C:19]2[S:20][C:21]([S:24](Cl)(=[O:26])=[O:25])=[C:22]([CH3:23])[C:18]=2[CH:17]=1>>[CH3:1][N:2]([CH3:14])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([NH:9][S:24]([C:21]2[S:20][C:19]3[CH:28]=[CH:29][C:16]([Cl:15])=[CH:17][C:18]=3[C:22]=2[CH3:23])(=[O:26])=[O:25])[CH:10]=[CH:11][C:12]=1[I:13]
Reactant: CN(C)CCOc1cc(N)ccc1I
Reactant: Cc1c(S(=O)(=O)Cl)sc2ccc(Cl)cc12
Product: Cc1c(S(=O)(=O)Nc2ccc(I)c(OCCN(C)C)c2)sc2ccc(Cl)cc12

Procedure:
The title compound was prepared from 3-(2-dimethylaminoethoxy)-4iodoaniline (WO95/15954, Description 50) (109 mg, 0.36 mmol) and 5-chloro-3-methylbenzo[b]thiophene-2-sulfonyl chloride (100 mg, 0.36 mmol) using the method of Example 1 (70 mg, 36%) MH+=551/553.
Reaction SMILES: [C:1]1([O:11][CH2:12][CH2:13][NH:14][C:15]2[CH:16]=[C:17]([CH:22]=[CH:23][CH:24]=2)[C:18]([O:20]C)=[O:19])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[K+].C(O)C.Cl>O>[C:1]1([O:11][CH2:12][CH2:13][NH:14][C:15]2[CH:16]=[C:17]([CH:22]=[CH:23][CH:24]=2)[C:18]([OH:20])=[O:19])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1cccc(NCCOc2cccc3ccccc23)c1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1cccc(NCCOc2cccc3ccccc23)c1

Procedure:
A solution of 3.2 g. of methyl 3-[2-(1-naphthyloxy)ethylamino]benzoate and 1.68 g. of potassium hydroxide in 40 ml. of 95% ethanol is heated to reflux for 4 hours. After cooling and diluting with 80 ml. of water, the solution is acidified with concentrated HCl and filtered. Recrystallization from acetonitrile affords the white desired product, m.p. 150°-152° C.
Reaction SMILES: C([Li])CCC.[CH3:6][S:7][CH2:8][P:9](=[O:16])([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12].[CH2:17]([C:21]1[CH:26]=[C:25](Cl)[N:24]2[N:28]=[CH:29][CH:30]=[C:23]2[N:22]=1)[CH2:18][CH2:19][CH3:20]>C1COCC1.C(OCC)(=O)C>[CH2:17]([C:21]1[CH:26]=[C:25]([CH2:6][S:7][CH2:8][P:9](=[O:16])([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])[N:24]2[N:28]=[CH:29][CH:30]=[C:23]2[N:22]=1)[CH2:18][CH2:19][CH3:20]
Reactant: CCCCc1cc(Cl)n2nccc2n1
Reactant: CCOP(=O)(CSC)OCC
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCc1cc(CSCP(=O)(OCC)OCC)n2nccc2n1
Temperature: -78 °C
Reaction time: 1 h
Yield: 66.6 %

Procedure:
30.7 ml of n-butyl lithium (1.63 M, n-hexane solution) was diluted with 35 ml of THF, and the diluted solution was cooled to −78° C. in an atmosphere of argon. Thereto was added a solution of 10.4 g of diethyl methylthiomethylphosphonate in 10 ml of THF, followed by stirring at −78° C. for 1 hour. Thereto was added dropwise a solution of 5 g of 5-n-butyl-7-chloropyrazolo[1,5-a]pyrimidine in 5 ml of THF, followed by stirring at −78° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed sequentially with aqueous ammonium chloride solution, water and saturated saline and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1). As a result, 5.9 g of diethyl (5-n-butylpyrazolo[1,5-a]pyrimidin-7-yl)methylthiomethylphosphonate was obtained as an oily product.
Reaction SMILES: [Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[B:13](OC)([O:16]C)[O:14]C.Cl>C1COCC1.O.C1COCC1>[F:6][C:7]1[C:12]([B:13]([OH:16])[OH:14])=[CH:11][CH:10]=[CH:9][N:8]=1
Reactant: COB(OC)OC
Reactant: Fc1ccccn1
Agent: Cl
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: OB(O)c1cccnc1F
Temperature: -78 °C
Reaction time: 4 h

Procedure:
800 ml (1.28 mol) of n-BuLi (1.6M in hexane) are added to a solution of 188 ml (1.32 mol) of TMP in 1,000 ml of THF at -78° C. under argon. After the mixture has been stirred for 45 minutes at this temperature, 120.4 g (1.24 mol) of 2-fluoropyridine in 200 ml of THF are added in the course of 3 minutes. After the mixture has been stirred for 4 hours at -78° C., a solution of 128.8 g (1.24 mol) of trimethyl borate in 200 ml of THF is added dropwise in the course of 20 minutes. Then, 200 ml of a 1: 1 mixture of water/THF is added at 25° C., and 256 ml of concentrated HCl are added dropwise, with ice-cooling. The organic phase is separated off, and the aqueous phase is washed twice using Et2O, filtered and concentrated in vacuo. Crude yield 148.2 g.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].N1C=CC=CC=1.[N+:19]([C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[C:25](Cl)=[O:26])([O-:21])=[O:20]>C(Cl)(Cl)Cl>[CH3:12][O:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:25](=[O:26])[C:24]2[CH:28]=[CH:29][CH:30]=[C:22]([N+:19]([O-:21])=[O:20])[CH:23]=2)=[C:3]([CH:7]=1)[C:4]([NH2:6])=[O:5]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: COc1ccc(N)c(C(N)=O)c1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COc1ccc(NC(=O)c2cccc([N+](=O)[O-])c2)c(C(N)=O)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 133.6 %

Procedure:
To a suspension of 2-amino-5-methoxybenzamide (2.42 g, 14.6 mmol) and pyridine (6 mL) in CHCl3 (120 mL) was added 3-nitrobenzoyl chloride (3.0 g, 16.1 mmol). The resulting mixture was stirred at RT for 6 h. The volatiles were removed in vacuo and the resultant solid was washed with Et2O to give the 5-Methoxy-2-(3-nitrobenzoyl)aminobenzamide (6.15 g) which was taken directly on to the next step. HPLC retention time 6.58 mins.