Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][N:12]=1)=[O:10].[O:17]1[C:21]([C:22]2[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=2)=[CH:20][N:19]=[CH:18]1>>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:28]([C:25]2[CH:26]=[CH:27][C:22]([C:21]3[O:17][CH:18]=[N:19][CH:20]=3)=[CH:23][CH:24]=2)(=[O:29])=[O:30])=[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][N:12]=2)=[O:10])[CH:4]=1
Reactant: O=S(=O)(Cl)c1ccc(-c2cnco2)cc1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccncn1
Product: O=C(c1ccncn1)c1cc(Cl)ccc1NS(=O)(=O)c1ccc(-c2cnco2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 116 mg of (2-Amino-5-chloro-phenyl)-pyrimidin-4-yl-methanone and 122 mg of 4-oxazol-5-yl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 7.43 (s, 1H), 7.53 (dd, 1H, J=8.8 Hz, 2.4 Hz), 7.62 (m, 2H), 7.75 (m, 2H), 7.80 (m, 3H), 7.98 (s, 1H), 8.99 (d, 1H, J=5.2 Hz), 9.25 (b, 1H), 10.29 (b, 1H). MS: m/z 441.9 (M++1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1.C([Li])CCC.Cl[Si:17]([CH2:20][Cl:21])([CH3:19])[CH3:18].O>O1CCCC1.CCCCCC.C(OCC)(=O)C>[Cl:21][CH2:20][Si:17]([C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[O:9][CH3:10])([CH3:19])[CH3:18]
Reactant: COc1cccc(OC)c1
Reactant: C[Si](C)(Cl)CCl
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: COc1cccc(OC)c1[Si](C)(C)CCl
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.5 %

Procedure:
A solution of 25.0 g (0.181 mol) of 1,3-dimethoxybenzene in 250 ml of tetrahydrofuran was stirred at room temperature under nitrogen while 125 ml (0.200 mol) of 1.6 molar n-butyllithium in hexane was added dropwise over 30 minutes. The resulting mixture was refluxed 1.5 hour, giving an orange-brown solution that was cooled to 5° and stirred while 27 ml (29.4 g, 0.205 mol) of chloro(chloromethyl)dimethylsilane was added dropwise over 15 minutes. The resulting white suspension was allowed to warm to room temperature, stirred there 1 hour, diluted with ethyl acetate, poured into water, and extracted with ether. The organic layers were washed with brine, dried over magnesium sulfate, and distilled to give 37.0 g (84%) of the title compound as a colorless liquid: bp 98°-110° (0.1 mm); nmr (CDCl3) 0.4 (6H, s), 3.1 (2H, s), 3.7 (6H, s), 6.3 (2 H, d), 7.1 (1H, m).
Reaction SMILES: C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[O:10][CH:11]=[C:12]([C:14](=[O:16])[NH2:15])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:38]2[C@H:39]([CH3:62])[C@H:40]3[C@@H:57]([C@H:58]([OH:60])[CH3:59])[C:56](=[O:61])[N:41]3[C:42]=2[C:43]([O:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=2)=[O:44])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.C(OCC)(=O)C>[C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:8][CH:5]([S:4][C:38]3[C@H:39]([CH3:62])[C@@H:40]4[C@@H:57]([C@H:58]([OH:60])[CH3:59])[C:56](=[O:61])[N:41]4[C:42]=3[C:43]([O:45][CH2:46][C:47]3[CH:48]=[CH:49][C:50]([N+:53]([O-:55])=[O:54])=[CH:51][CH:52]=3)=[O:44])[CH2:6]2)[O:10][CH:11]=1)(=[O:16])[NH2:15]
Reactant: CC(=O)SC1CN(c2nc(C(N)=O)co2)C1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@@H]12
Agent: NN
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(SC3CN(c4nc(C(N)=O)co4)C3)[C@H](C)[C@H]12
Temperature: 25 °C
Reaction time: 1 h
Yield: 50.5 %

Procedure:
To a solution of 3-acetylthio-1-(4-carbamoyl-1,3-oxazol-2-yl)azetidine (275 mg, 1.14 mmol) (obtained as described in Reference Example 22) in dimethylformamide (14 ml) was added hydrazine acetate (126 mg, 1.37 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (677 mg,1.14 mmol) in acetonitrile (14 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (0.79 ml, 4.56 mmol). The mixture was stirred overnight while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using toluene: acetonitrile: methanol (10:10:1) as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-oxazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (313 mg, yield 51%) as a pale yellow solid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2([CH3:29])[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:14][CH2:13]1.C(N(CC)CC)C>ClCCl>[CH3:29][C:18]1([N:15]2[CH2:16][CH2:17][C:12](=[O:11])[CH2:13][CH2:14]2)[CH2:19][CH2:20][N:21]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22][CH2:23]1
Reactant: CCOC(=O)N1CCC(C)(N2CCC(O)CC2)CC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CCOC(=O)N1CCC(C)(N2CCC(=O)CC2)CC1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 92.7 %

Procedure:
A solution of oxalyl chloride in dichloromethane (2M, 2.05 mL, 4.1 mmol) was cooled to −78° C. under nitrogen atmosphere and was added to a solution of dimethylsulfoxide (0.58 mL, 8.1 mmol) in dichloromethane (6 mL) at −78° C. under nitrogen atmosphere via cannula. After 10 minutes, a solution of ethyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate (2.7 mmol) in dichloromethane (3 mL) was added at −78° C. under nitrogen atmosphere to the reaction mixture via cannula. The mixture was stirred at −78° C. for 10 minutes and then triethylamine (1.51 mL, 10.8 mmol) was added dropwise. The reaction was stirred at −78° C. under nitrogen atmosphere for another 20 minutes, and then allowed to warm up to 0° C. over 1 hour. The reaction was quenched with water (10 mL) and diluted with dichloromethane (30 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×25 mL). The combined organic phases were washed with saturated aqueous ammonium chloride, brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound as yellow oil (672 mg, 93%), which was used for the subsequent step without further purification. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.96 (s, 3H), 1.24-1.30 (m, 3H), 1.39-1.53 (m, 2H), 1.72-1.92 (m, 2H), 2.11-2.30 (m, 1H), 2.42 (t, J=5.86 Hz, 2H), 2.51 (t, J=6.05 Hz, 1H), 2.81 (t, J=5.86 Hz, 2H), 2.97 (t, J=6.05 Hz, 1H), 3.22 (t, J=12.01 Hz, 1H), 3.35-3.47 (m, 2H), 3.53-3.72 (m, 2H), 4.14 (q, J=7.10 Hz, 2H). MS (M+1): 269.24.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[C:6]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[C:4](=[O:20])[N:3]1[CH:21]1[CH2:26][CH:25]([O:27]C(=O)C)[C:24](=[O:31])[NH:23][C:22]1=[O:32].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([NH:11][C:12](=[O:19])[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:7]=[CH:8][CH:9]=2)[C:4](=[O:20])[N:3]1[CH:21]1[CH2:26][CH:25]([OH:27])[C:24](=[O:31])[NH:23][C:22]1=[O:32]
Reactant: CC(=O)OC1CC(N2C(=O)c3cccc(NC(=O)c4ccccc4)c3C2=O)C(=O)NC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Product: O=C(Nc1cccc2c1C(=O)N(C1CC(O)C(=O)NC1=O)C2=O)c1ccccc1

Procedure:
A solution of 3-[1,3-dioxo-4-benzamidoisoindolin-2-yl]-2,6-dioxo-5-acetoxypiperidine (1.36 g, 3.5 mmol) and p-toluenesulfonic acid (0.33 g, 1.8 mmol) in methanol (20 mL) is heated at reflux for 5 hours. The solvent is removed in vacuo to give 3-[1,3-dioxo-4-benzamidoisoindolin-2-yl]-2,6-dioxo-5-hydroxypiperidine which is further purified by column chromatography.
Reaction SMILES: [CH2:1]([S:6][C:7]1[S:8][C:9]2[CH:15]=[C:14]([S:16]([N:19]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:20]([CH3:24])[C:21](O)=[O:22])(=[O:18])=[O:17])[CH:13]=[CH:12][C:10]=2[N:11]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C(Cl)(=O)C(Cl)=O.Cl.[OH:39][NH2:40].C([O-])(O)=O.[Na+].C1COCC1.O>>[OH:39][NH:40][C:21](=[O:22])[C@H:20]([N:19]([S:16]([C:14]1[CH:13]=[CH:12][C:10]2[N:11]=[C:7]([S:6][CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[S:8][C:9]=2[CH:15]=1)(=[O:18])=[O:17])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[CH3:24]
Reactant: NO
Reactant: CCCCCSc1nc2ccc(S(=O)(=O)N(Cc3ccccc3)[C@H](C)C(=O)O)cc2s1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Solvent: C1CCOC1
Solvent: O
Product: CCCCCSc1nc2ccc(S(=O)(=O)N(Cc3ccccc3)[C@H](C)C(=O)NO)cc2s1

Procedure:
Using various N-benzylsulfonyl acid derivatives as a starting material obtained in Example 33, the following titled compounds were prepared by applying the above method under the condition of oxalylchloride/hydroxyamine hydrochloride/NaHCO3/THF/H2O.
Reaction SMILES: O[CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(S(F)(F)[F:21])CC>ClCCl>[F:21][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1
Reactant: CCN(CC)S(F)(F)F
Reactant: CC(C)(C)OC(=O)C1CCC(O)CC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)C1CCC(F)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 25 %

Procedure:
To a solution of tert-butyl 4-hydroxycyclohexanecarboxylate (1500 mg, 7.45 mmol) in dichloromethane (anhydrous, 20 ml), DAST was (1571 mg, 22.4 mmol) added at 0° C. The resulting mixture was stirred at 0° C. for 3 hours. The mixture was diluted with dichloromethane, quenched with sodium bicarbonate. The organic layer was separated, the aqueous phase was extracted with EtOAc. The combined organic layer were washed with water, brine, dried with androus sodium sulphate. The product was purified (flash chromatography, 10 to 20% EtOAc/hexanes) and obtained as a 210 mg of yellow oil (25%). 1H NMR (300 MHz, CDCl3): δ 5.60-5.80 (m, 1H), 4.99-5.09 (m, 2H), 4.73 (d, 2H), 3.34 (br, 2H), 2.29-2.32 (m, 2H), 1.44-1.46 (m, 9H).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[O:11][C:12]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([F:18])[C:14]=1B(O)O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:23][C:24]1[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]([OH:34])[C:27](Br)=[CH:26][CH:25]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:23][C:24]1[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]([OH:34])[C:27]([C:14]2[C:13]([F:18])=[C:12]([Si:19]([CH3:22])([CH3:21])[CH3:20])[O:11][C:10]=2[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:26][CH:25]=1
Reactant: COC(=O)c1c(N)ccc(Br)c1O
Reactant: CC(C)(C)[Si](C)(C)OCc1oc([Si](C)(C)C)c(F)c1B(O)O
Agent: [Pd]
Agent: CC(C)(C)[PH+](C(C)(C)C)C(C)(C)C
Agent: F[B-](F)(F)F
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1c(N)ccc(-c2c(CO[Si](C)(C)C(C)(C)C)oc([Si](C)(C)C)c2F)c1O
Temperature: 63 °C
Yield: 47.6 %

Procedure:
A mixture of 2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid (Intermediate 103, 6.0 g), methyl 6-amino-3-bromo-2-hydroxybenzoate (prepared according to Wang et al, Bioorg Med Chem Lett 2007 17 2817, 4.27 g), tris-(dibenzylideneacetone)dipalladium (0.793 g), tri-tert-butylphosphonium tetrafluoroborate (0.502 g) and cesium carbonate (16.94 g) in dioxane (96 mL) and water (12 mL) was heated at 63° C., under an atmosphere of nitrogen for 90 minutes. The mixture was cooled and diluted with ethyl acetate, washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-20%. The resultant product was re-purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane, with a gradient of 0-100% to give methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoate (3.86 g) as a yellow oil which crystallised with scratching to give an off-white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[Li]CCCC.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27]Br)[CH:23]=[CH:24][CH:25]=1>C1COCC1.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:27][CH2:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[CH:21]=2)[C:10]([OH:12])=[O:11])=[CH:7][CH:8]=1
Reactant: COc1ccc(CC(=O)O)cc1
Reactant: COc1cccc(CCBr)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COc1ccc(C(CCc2cccc(OC)c2)C(=O)O)cc1
Temperature: -70 °C
Reaction time: 1.5 h

Procedure:
4-Methoxyphenylacetic acid (50.68 g, 305 mmol) was dissolved in 1.4 L of THF and cooled to -70° C. under a nitrogen atmosphere. 400 mL of 1.6M (640.5 mmol) of n-BuLi in hexane was slowly added. 72.1 g (335.5 mmol) of 2-(3-methoxyphenyl)ethylbromide in 400 mL of THF was slowly added and the reaction allowed to proceed for 1.5 hours. The reaction was allowed to warm to ambient temperature. The reaction was quenched with 500 mL of 0.5N NaOH and heated to 50° C. for one hour and cooled to ambient temperature. The reaction mixture was extracted three times with ether, the aqueous layer was acidified with 150 mL of 5N HCl and extracted twice with CHCl3. The CHCl3 extract was washed twice with brine, dried with Na2SO4, and evaporated to a yellow solid. This yielded 78.2 g of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.I[C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=1>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=2)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(I)cc1[N+](=O)[O-]
Reactant: Cc1ccc(I)cc1
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Product: Cc1ccc(-c2ccc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])c2)cc1

Procedure:
Prepared from (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example A1), bis(pinacolato)diboron and 4-iodotoluene according to the general procedure C. Obtained as an orange solid (542 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:13][Sn:14](Cl)([CH3:16])[CH3:15].[Cl-].[NH4+]>CCCCCC.C1C=CC=CC=1.CCOCC.O>[CH3:13][Sn:14]([CH3:16])([CH3:15])[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Brc1cccnc1
Reactant: C[Sn](C)(C)Cl
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOCC
Solvent: c1ccccc1
Product: C[Sn](C)(C)c1cccnc1
Temperature: -50 °C
Reaction time: 1 h

Procedure:
To a reaction vessel equipped with a mechanically driven agitator, water-cooled condenser, addition funnel, thermometer, and nitrogen inlet was added a solution containing 17.1 g. (0.108 mole) of 3-bromopyridine in 150 cc. of anhydrous ether. The solution was cooled to -50° C. using a dry ice-acetone bath. By a dropwise addition, 40 cc. (0.108 mole) of n-butyllithium in n-hexane was added over 14 minutes. The resulting yellow-orange solution was stirred for an additional 60 minutes. A solution containing 17.9 g. (0.09 mole) of trimethyltin chloride in 150 cc. of anhydrous benzene was added over 40 minutes, followed by a 75 minute stirring period. The dark orange solution was warmed to room temperature and stirred 18 hours before being hydrolyzed with a saturated aqueous solution of ammonium chloride. The aqueous phase was separated from the organic phase and washed with 200 cc. of ether. The organic portions were combined, dried over a quantity of anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. A dark red liquid (16.2 g.) was isolated and distilled under reduced pressure (0.1-0.2 mm.). A clear, colorless liquid fraction boiling at 50°-60° C. was collected and redistilled (6.5 mm.). The fraction boiling at 100°-103° C. was collected and analyzed. The tin content was found to be 48.89%. The calculated tin content for trimethyl-3-pyridyltin is 49.07%. Gas chromatographic analysis indicated a purity of 98% and the refractive index was recorded as 1.5399 at 25° C. The nuclear magnetic resonance spectrum contained a singlet at 0.33 ppm. (CH3 -Sn, 9H's), a complex multiplet centered at 7.2 ppm. (β-pyridyl H, 1H), a doublet of triplets at 7.75 ppm. (γ-pyridyl H, 1H), a doublet of doublets at 8.52 ppm. (γ-pyridyl H on 6 carbon, 1H), and a doublet at 8.65 ppm. (γ-pyridyl H on 2 carbon, 1H), in agreement with the expected structure.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[N:12]=[CH:13][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:7]1[N:6]([CH3:20])[C:5]2=[O:21].[C:22]1([N:28]=[C:29]=[S:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.N1C=CC=CC=1>O>[CH3:20][N:6]1[C:5](=[O:21])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:29]([NH:28][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[S:30])[CH:3]=2)[N:8]2[N:12]=[CH:13][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:7]12
Reactant: S=C=Nc1ccccc1
Reactant: CCOC(=O)c1cnn2c3ccc(N)cc3c(=O)n(C)c12
Solvent: O
Solvent: c1ccncc1
Product: CCOC(=O)c1cnn2c3ccc(NC(=S)Nc4ccccc4)cc3c(=O)n(C)c12

Procedure:
A solution of 5 g. (0.018 mole) of ethyl 7-amino-4-methyl-4,5-dihydro-5-oxopyrazolo[1,5-a]quinazoline-3-carboxylate and 2.4 g. (0.018 mole) of phenyl isothiocyanate in 250 ml. of pyridine was stirred and heated on a steam bath for about 2 hours, then cooled and diluted with water. The solid which separated was collected to give crude ethyl 4-methyl-7-phenylthioureido-4,5-dihydro-5-oxopyrazolo[1,5-a]quinazoline-3-carboxylate which was not further purified but used as such in Example 7T.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1.C([N-]C(C)C)(C)C.[Li+].[C:23]1(=[O:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.O>O1CCCC1.C(OCC)(=O)C>[OH:30][C:23]1([CH:6]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[C:2]2[NH:1][CH:5]=[CH:4][N:3]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: N#Cc1ccc(Cc2ncc[nH]2)cc1
Reactant: O=C1CCCCCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: N#Cc1ccc(C(c2ncc[nH]2)C2(O)CCCCCC2)cc1
Reaction time: 0.5 h
Yield: 99.2 %

Procedure:
10 g of 4-[1-(imidazolyl)methyl]benzonitrile is dissolved in 270 ml of tetrahydrofuran and combined at -50° with 40 ml of 1.5-molar solution of lithium diisopropylamide in tetrahydrofuran, stirred for 0.5 hour at -60°, combined with 6.5 g of cycloheptanone, stirred further for 1 hour, and heated to 25°. Then water is added, the mixture is diluted with ethyl acetate, washed neutral with water, dried over sodium sulfate, and concentrated to dryness under vacuum, thus producing 16 g of crude 4-[1-hydroxycyclohept-1-yl-1-(imidazolyl)methyl]benzonitrile.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:21]([S:30][CH3:31])=[CH:20][N:19]=2)=[CH:14][CH:13]=1)=S.C1(N=C=NC2CCCCC2)CCCCC1>C1COCC1>[CH3:31][S:30][C:21]1[C:22]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[N:23][C:18]([C:15]2[CH:16]=[CH:17][C:12]([NH:11][C:9]3[NH:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[N:1]=3)=[CH:13][CH:14]=2)=[N:19][CH:20]=1
Reactant: CSc1cnc(-c2ccc(NC(=S)Nc3ccccc3N)cc2)nc1N1CCOCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Product: CSc1cnc(-c2ccc(Nc3nc4ccccc4[nH]3)cc2)nc1N1CCOCC1
Temperature: 64 °C
Yield: 72.4 %

Procedure:
A suspension of 1-(2-aminophenyl)-3-(4-(5-(methylthio)-4-morpholinopyrimidin-2-yl)phenyl)thiourea (60 mg, 0.132 mmole) and dicyclohexylcarbodiimide (31 mg, 0.15 mmole) in THF (5 ml) was heated at 64° C. for 20 hr. The cooled mixture was purified by flash chromatography to give a product (40 mg, 73%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([CH:23]3[CH2:28][CH2:27][N:26]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH2:25][CH2:24]3)=[O:22])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[N:11]1([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]([CH:23]3[CH2:24][CH2:25][N:26]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH2:27][CH2:28]3)=[O:22])=[CH:18][CH:19]=2)[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: COC(=O)CN1CCC(C(=O)Nc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)cc2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)CN1CCC(C(=O)Nc2ccc(N3CCNCC3)cc2)CC1
Yield: 92.5 %

Procedure:
A solution of Methyl 4-[[[4-(4-t-butyloxycarbonyl-1-piperazinyl)phenyl]amino]carbonyl]-1-piperidine acetate (2.1 g, 4.5 mmol) was treated with CH2Cl2 /TFA (10 mL/15 mL) for 20 min. Solution was concentrated and the residue was treated with MeOH/4M HCl (10 mL/10 mL). Solution was concentrated until precipitation started. Solution was filtered and the solid was washed with Et2O to give the title compound (1.5 g, 87%). MS (ES) m/e 361 [M+H]+. 1HNMR (250 MHz, DMSO[d6]) δ 1.4-4.5 (m, 22H), 6.9-9.5 (m, 5H). Anal. (C18H25N3O3.2.87HCl.0.5H2O) calcd: C, 54.32; H, 7.20; N, 10.29. found: C, 54.52; H, 7.24; N, 10.35.
Reaction SMILES: C(N[C@@H]1CCCC[C@H]1NCC1C=CC=CC=1)C1C=CC=CC=1.C(O[SiH](OCC)OCC)C.[C:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)(=[O:35])[CH3:34]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:36]1([CH:33]([OH:35])[CH3:34])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CC(=O)c1ccccc1
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: CCO[SiH](OCC)OCC
Solvent: C1CCOC1
Product: CC(O)c1ccccc1
Temperature: 45 °C
Reaction time: 0.5 h
Yield: 73 %

Procedure:
Titanium (IV) isopropoxide (30μL, 0.10 mmol) was added to a solution of (R,R)-1,2-bis(benzylamino)cyclohexane(29μL, 0.10 mmol) and triethoxysilane (370μL, 2.00 mmol) in THF (6 mL) under an argon atmosphere, followed by rinsing with THF (1 mL). After 30 minutes at room temperature, the mixture was heated rapidly to the reflux temperature, then allowed to cool slowly to 45° C. The mixture turned a dark bluish color. Then acetophenone (118μL, 1.01 mmol) was added. The mixture gradually decolorized, then returned to the dark color. After 16 hours the reaction mixture was quenched with 15% NaOH (4mL). The mixture was diluted with THF and water and allowed to stir vigorously. It became colorless. Five hours later, GC on a poly(phenylmethylsiloxane) column showed the mixture consisted of 96% 1-phenylethanol and 2% acetophenone (the proportion of the diamine was not determined), and GC on a chiral Cyclodex B column showed that the alcohol had an ee of 8% in favor of the (S) enantiomer. The reaction mixture was diluted with ether, and the organic layer was washed with a mixture of 1 N HCl and brine, dried over MgSO4, evaporated, and dried in vacuo to give 1-phenylethanol, pure by 1H NMR, in 73% yield.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][C:14]#[N:15].[H][H]>[Co].C(O)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][NH2:15]
Reactant: Cc1oc(-c2ccccc2)nc1CC#N
Reactant: [H][H]
Agent: [Co]
Solvent: CCO
Product: Cc1oc(-c2ccccc2)nc1CCN
Yield: 125.8 %

Procedure:
6.00 g (30 mmol) of (5-Methyl-2-phenyl-oxazol-4-yl)-acetonitrile were hydrogenated in the presence of 0.60 g of wet Raney Cobalt catalyst (Blackwell-Catalloy, Type Nr. 1708042) in 54 mL of ethanol in a 185 mL stainless steel autoclave under 9 bar of hydrogen pressure at 70° C. for 3 h. Removal of the catalyst by filtration, evaporation of the solvents and work-up as in example 1 afforded 7.63 g of 2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethylamine as its mesylate salt with a purity of 100% (HPLC area %).