Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[NH:12][C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33]>C(OCC)(=O)C.O>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][N:12]1[C:11]2[N:10]=[CH:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:16]=2[C:15](=[O:17])[NH:14][C:13]1=[O:18])[CH3:36]
Reactant: CCOC(=O)CBr
Reactant: O=c1[nH]c(=O)c2c(ncn2Cc2ccccc2)[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1c(=O)[nH]c(=O)c2c1ncn2Cc1ccccc1
Temperature: 40 °C
Yield: 44.1 %

Procedure:
A mixture of 7-benzyl-3,7-dihydropurine-2,6-dione (3.0 g), anhydrous potassium carbonate (2.0 g), and N,N-dimethylformamide (60 ml) was stirred with heating in an oil bath of 40° C., and ethyl bromoacetate (1.5 g) was added thereto. The mixture was stirred by heating at the same temperature for 4 hours. The reaction mixture was diluted with ethyl acetate and water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 20–40% (20% 2-propanol/ethyl acetate)/hexane to give 1.3 g of the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]([C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[C:13]#[N:14])=[O:9])=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[C:24](=[S:26])=[S:25].Br[CH2:28]Br>CS(C)=O.O>[S:25]1[CH2:28][S:26][C:24]1=[C:7]([C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)[C:8]([C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=1)[C:13]#[N:14])=[O:9]
Reactant: S=C=S
Reactant: BrCBr
Reactant: N#Cc1cccc(C(=O)Cc2ccncc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1cccc(C(=O)C(=C2SCS2)c2ccncc2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.1 %

Procedure:
To a solution of 3-(pyridin-4-yl-acetyl)-benzonitrile (12.5 g, 56 mmol) in dry DMSO (280 mL) under nitrogen atmosphere solid potassium carbonate (23.36 g, 169 mmol, 3 eq) was added at room temperature, followed by carbon disulfide (10.2 mL, 169 mmol, 3 eq) and dibromomethane (11.86 mL, 169 mmol, 3 eq). The reaction mixture was stirred at room temperature for 2 hours and then poured into stirred iced water (1.5 L mL). The orange precipitate was filtered, washed with water and dried at 60° C. under reduced pressure for 1 hour. The crude product was purified by silica gel chromatography (SP1, eluant: n-hexane/ethyl acetate 2:8) to obtain 10.1 g of yellow solid (58%).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[F:7][C:8]([F:18])([F:17])[C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH2:12][Br:13].C(OCC)C>ClCCCl>[Br-:13].[CH3:1][N+:2]1[CH:6]=[CH:5][N:4]([CH2:12][C:11]2[CH:14]=[CH:15][CH:16]=[C:9]([C:8]([F:7])([F:17])[F:18])[CH:10]=2)[CH:3]=1
Reactant: Cn1ccnc1
Reactant: FC(F)(F)c1cccc(CBr)c1
Solvent: CCOCC
Solvent: ClCCCl
Product: C[n+]1ccn(Cc2cccc(C(F)(F)F)c2)c1
Product: [Br-]
Yield: 55.9 %

Procedure:
In a 25 ml one-necked flask, 1.4 g (17.05 mmol) of 1-methylimidazole are dissolved in 15 ml of 1,2-dichloroethane and then 4.89 g (20.46 mmol) of 3-trifluoromethylbenzyl bromide are added. After heating overnight at 80°, 50 ml of diethyl ether are added. The oil, which is then separated by decantation, is crystallized from a mixture of ethyl acetate and tetrahydrofuran (2/1 by volume). The crystals thus obtained are drained and then dried under reduced pressure. 3.06 g (56%) of 1-methyl-3-(3-trifluoromethylbenzyl)imidazolium bromide are thus obtained in the form of off-white crystals, used as they are in the next step, whose characteristic is the following:
Reaction SMILES: C(N(CC)CC)C.[C:8]([C:10]1[CH:11]=[C:12]([N:16]=[C:17]=[S:18])[CH:13]=[CH:14][CH:15]=1)#[N:9].[C:19]([O:23][C:24](=[O:27])[CH2:25][NH2:26])([CH3:22])([CH3:21])[CH3:20]>ClCCl>[C:8]([C:10]1[CH:11]=[C:12]([NH:16][C:17]([NH:26][CH2:25][C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:27])=[S:18])[CH:13]=[CH:14][CH:15]=1)#[N:9]
Reactant: CC(C)(C)OC(=O)CN
Reactant: N#Cc1cccc(N=C=S)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CNC(=S)Nc1cccc(C#N)c1
Temperature: 20 °C
Reaction time: 12 h
Yield: 88.7 %

Procedure:
2.8 cm3 (20 mmol) of triethylamine and 3.2 g (20 mmol) of 3-cyanophenyl isothiocyanate are added at 0° C. to a solution of 3.35 g (20 mmol) of glycine t-butyl ester in 150 cm3 of dichloromethane. The mixture is stirred at 20° C. for 12 hours before being concentrated under vacuum and then taken up with a mixture of water and ethyl ether (300:300). The ether phase is separated off and washed with a 1N hydrogen chloride solution (200 cm3), and then with a saturated sodium chloride solution. After drying with magnesium sulfate and concentration under vacuum, 5.17 g (89% yield) of a yellow solid is obtained, whose melting point is 131°-132° C.
Reaction SMILES: [NH2:1][CH:2]([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:47][C:48]1[CH:49]=[C:50]([CH:60]=[C:61]([F:63])[CH:62]=1)[CH2:51][NH:52][C:53](=[O:59])[CH:54]([CH3:58])[C:55](O)=[O:56].CC#N>CN(C=O)C.C(O)(C(F)(F)F)=O>[F:47][C:48]1[CH:49]=[C:50]([CH:60]=[C:61]([F:63])[CH:62]=1)[CH2:51][NH:52][C:53](=[O:59])[CH:54]([CH3:58])[C:55]([NH:1][CH:2]([CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4])=[O:56]
Reactant: NC(Cc1c[nH]c2ccccc12)C(=O)N1CCc2ccccc2C1
Reactant: CC(C(=O)O)C(=O)NCc1cc(F)cc(F)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: CC#N
Product: CC(C(=O)NCc1cc(F)cc(F)c1)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)N1CCc2ccccc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-(1H-indol-3-yl)-propan-1-one (57 mg, 0.18 mmol) was placed in a disposable polypropylene tube and dissolved in DMF (1 ml). TBTU (O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-tetrafluoroborate, 65 mg, 0.2 mmol) and N-(3,5-difluoro-benzyl)-2-methyl-malonamic acid (49 mg, 0.2 mmol) were added, and the mixture was shaken overnight at r.t. The title compound, MS: m/e=545.3 (M+H+), was isolated from the reaction mixture by automated, preparative HPLC (YMC CombiPrep C18 column 50×20 mm, solvent gradient 5-95% CH3CN in 0.1% TFA(aq) over 6.0 min, λ=230 nm, flow rate 40 ml/min).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([Cl:14])=[N:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:4][N:3]=1.[CH3:15][NH2:16]>C(Cl)Cl.C1COCC1.CC(C)=O>[Cl:14][C:9]1[C:8]([C:6]2[N:5]=[CH:4][N:3]=[C:2]([NH:16][CH3:15])[N:7]=2)=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: CN
Reactant: Clc1ncnc(-c2cccnc2Cl)n1
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: CNc1ncnc(-c2cccnc2Cl)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To 2-chloro-4-(2-chloro-pyridin-3-yl)-[1,3,5]triazine (10.0 g, 44.0 mmol) in 55 ml of methylene chloride was added methylamine (45 ml, 88.0 mmol) as a 2.0 M solution in THF at 0° C. After stirring at room temperature for 18 h, the mixture was diluted with acetone and filtered through a plug of silica gel and concentrated to yield the title compound. MS m/z=222 [M+H]+. Calc'd for C9H8ClN5: 221.65.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[N:9]([C:10]=1[C:11]([C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=1)=[O:12])[CH:8]=[CH:7][CH:6]=[CH:5]2.O.C(O)C>[Zn].C(O)(=O)C>[NH2:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([C:10]2[N:9]3[C:4]([CH:5]=[CH:6][CH:7]=[CH:8]3)=[CH:3][C:2]=2[CH3:1])=[O:12])=[CH:18][CH:17]=1
Reactant: Cc1cc2ccccn2c1C(=O)c1ccc([N+](=O)[O-])cc1
Agent: [Zn]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc2ccccn2c1C(=O)c1ccc(N)cc1
Temperature: 80 °C
Yield: 81.4 %

Procedure:
5.66 g (86.57 mmol) of zinc and 20.63 ml (360.71 mmol) of glacial acetic acid are added to 6.74 g (24.05 mmol) of (2-methylindolizin-3-yl)(4-nitrophenyl)methanone in 120 ml of a 2/1 mixture of water and ethanol. The reaction medium is heated at 80° C. for 4 hours. 0.57 g (8.7 mmol) of zinc and 2.06 ml of glacial acetic acid are added. Refluxing is maintained for 1 hour. At ambient temperature, the reaction medium is filtered off. The residue obtained is rinsed with ethyl acetate and with methyl THF. The organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate and then with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, and then concentrated under reduced pressure. The residue obtained is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (90/10) mixture. 4.9 g of a yellow solid are obtained.
Reaction SMILES: [CH2:1]([O:8][N:9]([CH2:12][C:13]1[CH:18]=[C:17]([Cl:19])[C:16]([OH:20])=[C:15]([Cl:21])[CH:14]=1)[CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22](O)[CH2:23][CH2:24][CH3:25].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C(Cl)Cl>[CH2:1]([O:8][N:9]([CH2:12][C:13]1[CH:14]=[C:15]([Cl:21])[C:16]([O:20][CH2:22][CH2:23][CH2:24][CH3:25])=[C:17]([Cl:19])[CH:18]=1)[CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCO
Reactant: O=CN(Cc1cc(Cl)c(O)c(Cl)c1)OCc1ccccc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCOc1c(Cl)cc(CN(C=O)OCc2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of N-benzyloxy-N-(3,5-dichloro-4-hydroxybenzyl)formamide in methylene chloride (5 ml) was added n-butanol (110 ul, 1.2 mmol) and Polymer-bound triphenyl phosphine resin (500 mg, 1,2 mmol/g, 0.6 mmol). The reaction mixture was stirred for 0.5 h at room temperature then cooled to 0° C. A solution of DEAD (0.6 mmol, 95 ul) in methylene chloride (1 ml) was added and the reaction mixture stirred at room temperature for 16 h. The resin was filtered and washed with methylene chloride three times and the filtrate was evaporated to afford the crude N-benzyloxy-N-(4-butoxy-3,5-dichlorobenzyl)formamide as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.38 (m, 3H), 7.28 (m, 2H), 7.19 (s, 2H), 4.78 (s, 2H), 4.57 (s, 2H), 4.00 (t, j=6.4 Hz, 2H), 1.82 (quint, j=7.6 Hz, 2H), 1.55(sext, j=7.6 Hz, 2H), 0.98 (t, j=7.6 Hz, 3H). M+1=382
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:22]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:28]([OH:30])=O)=[N:17][C:18]=4[CH2:19][CH2:20]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[OH:31][C@@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:22]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:28]([N:34]5[CH2:35][CH2:36][C@@H:32]([OH:31])[CH2:33]5)=[O:30])=[N:17][C:18]=4[CH2:19][CH2:20]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: N#Cc1ccc(N2N=C3c4ccc(C(=O)O)nc4CCC3C2C2CCCC2)cc1Cl
Reactant: O[C@@H]1CCNC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: N#Cc1ccc(N2N=C3c4ccc(C(=O)N5CC[C@@H](O)C5)nc4CCC3C2C2CCCC2)cc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 61.4 %

Procedure:
In a dried reaction flask, 2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-pyrazolo[3,4-f]quinoline-7-carboxylic acid (0.421 g, 1.0 mmol), (R)-3-hydroxylpyrrolidine (0.113 g, 1.3 mmol), DIEA(0.2 mL, 1.15 mmol), and HATU (0.418 g, 1.1 mmol) were added to a mixed solvent of DMF (4 mL) and dichloromethane (8 mL). The mixture was stirred at room temperature for 2 hr and the solution was concentrated under reduced pressure. Water was added to the residue. The mixture was filtered to obtain a crude yellow solid, which was washed with methanol to obtain a purified product (0.301 g) in 61.4% yield.
Reaction SMILES: [CH:1](O)=[O:2].C(O[C:8](=[O:10])[CH3:9])(=O)C.[NH2:11][C:12]1[S:13][CH:14]=[C:15]([O:19][CH2:20][CH3:21])[C:16]=1[C:17]#[N:18]>O>[CH:1]([NH:11][C:12]1[S:13][CH:14]=[C:15]([O:19][CH2:20][CH3:21])[C:16]=1[C:17]#[N:18])=[O:2].[CH2:8]([OH:10])[CH2:9][CH2:14][CH2:15][CH3:16]
Reactant: CC(=O)OC(C)=O
Reactant: O=CO
Reactant: CCOc1csc(N)c1C#N
Solvent: O
Product: CCCCCO
Product: CCOc1csc(NC=O)c1C#N
Temperature: 50 °C
Reaction time: 4 h

Procedure:
200 parts of formic acid are added dropwise to 500 parts of acetic anhydride at room temperature, and 168 parts of 2-amino-3-cyano-4-ethoxythiophene are introduced after 2 hours. The mixture is stirred for 4 hours at 50° C., after which 1000 parts of water are run into the hot mixture. The mixture is cooled and the product is then filtered off under suction, washed with water and dried. 174 parts of 2-formylamino-3-cyano-4-ethoxythiophene of melting point 191°-192° C. (from pentanol) are obtained.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([C:10]2[NH:11][CH:12]=[CH:13][CH:14]=2)=O)=[CH:6][CH:5]=[CH:4][N:3]=1.O.[NH2:16][NH2:17]>C(O)C>[NH:11]1[CH:12]=[CH:13][CH:14]=[C:10]1[C:8]1[C:7]2[C:2](=[N:3][CH:4]=[CH:5][CH:6]=2)[NH:17][N:16]=1
Reactant: NN
Reactant: O=C(c1ccc[nH]1)c1cccnc1Cl
Solvent: O
Solvent: CCO
Product: c1c[nH]c(-c2n[nH]c3ncccc23)c1
Yield: 81 %

Procedure:
A mixture of (2-chloro-pyridin-3-yl)-(1H-pyrrol-2-yl)-methanone (1 g, 4.8 mmol) and hydrazine hydrate (0.5 mL) in ethanol (15 mL) was heated to reflux for overnight. The reaction was concentrated and the residue was triturated with dichloromethane (to remove any unreacted starting material. The solid was filtered, washed wit water and dried to give 720 mg (81%) of the titled compound as a light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]3[CH2:14][CH2:15][CH2:16][CH2:17][C@@H:10]3[CH2:9]2)=[CH:4][CH:3]=1.[CH2:18]1[O:26][C:25]2[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=2[O:19]1>>[ClH:1].[ClH:1].[O:19]1[C:20]2[CH:21]=[CH:22][C:23]([C:2]3[N:7]=[N:6][C:5]([N:8]4[CH2:13][CH2:12][N:11]5[CH2:14][CH2:15][CH2:16][CH2:17][C@@H:10]5[CH2:9]4)=[CH:4][CH:3]=3)=[CH:24][C:25]=2[O:26][CH2:18]1
Reactant: Clc1ccc(N2CCN3CCCC[C@@H]3C2)nn1
Reactant: OB(O)c1ccc2c(c1)OCO2
Product: Cl
Product: c1cc2c(cc1-c1ccc(N3CCN4CCCC[C@@H]4C3)nn1)OCO2

Procedure:
The title compound was prepared by a similar procedure to that described in Example 57, starting from (R)-2-(6-chloropyridazin-3-yl)octahydropyrido[1,2-a]pyrazine and 3,4-methylenedioxyphenylboronic acid.
Reaction SMILES: [C:1]1([CH3:8])[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][C:10](=[CH2:13])[CH2:11][OH:12].C=O.[CH2:16](NCCCC)CCC.C(O)(=O)C>>[CH3:13][C:10]1([CH2:11][OH:12])[CH2:9][CH2:16][C:5]2[C:6](=[C:1]([CH3:8])[CH:2]=[CH:3][CH:4]=2)[O:7]1
Reactant: Cc1ccccc1O
Reactant: C=C(C)CO
Reactant: CCCCNCCCC
Agent: C=O
Solvent: CC(=O)O
Product: Cc1cccc2c1OC(C)(CO)CC2
Temperature: 170 °C
Reaction time: 6 h

Procedure:
A pressure-proof reaction vessel equipped with a stirrer was charged with 16.2 g (0.15 mole) of o-cresol, 54.1 g (0.75 mole) of 2-methyl-2-propen-1 -ol, 6.2 g (0.165 mole) of 80% paraformaldehyde, 1.9 g (0.01 5 mole) of dibutylamine and 4.5 g (0.075 mole) of acetic acid, and the mixture was reacted, with stirring, at 170° C. for 6 hours.
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([OH:20])=O)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:34][OH:35].C(N)C>O1CCCC1.CN(C)C=O>[OH:35][NH:34][C:18]([CH2:17][CH2:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:11][CH:12]=1)=[O:20]
Reactant: O=C(O)CCc1ccc(NC(=O)c2ccccc2)cc1
Reactant: NO
Agent: CCN
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: O=C(CCc1ccc(NC(=O)c2ccccc2)cc1)NO
Temperature: 25 °C
Reaction time: 1 h
Yield: 72 %

Procedure:
(Method H7) To a solution of 3-(4-benzoylamino-phenyl)-propionic acid (6b) (1.04 g, 3.86 mmol) in tetrahydrofuran (30 ml) under argon atmosphere 1,1′-carbonyldiimidazole (0.814 g, 5.0 mmol), was added and the mixture was stirred at room temperature for 1 hour. In an another vessel, a solution of hydroxylamine hydrochloride (0.805 g, 11.6 mmol) in dimethylformamide (10 ml) was treated with ethyl amine (1.62 ml, 11.6 mmol), the precipitate was filtered off and both solutions were mixed together. The resultant mixture was stirred at ambient temperature for 24 hours, concentrated under reduced pressure and diluted with 3% hydrochloric acid (15 ml). The resulting precipitate was filtered, washed with water (3×20 ml), and crystallized from acetonitrile to give the title compound as a white solid (0.790 g, 72%). M.p. 189-191° C. 1H NMR (DMSO-d6, HMDSO) δ: 2.26 (t, 2H, J=7.5 Hz); 2.79 (t, 2H, J=7.5 Hz); 7.17 (d, 2H, J=8.4 Hz); 7.45-7.60 (m, 3H); 7.67 (d, 2H, J=8.4 Hz); 7.88-8.02 (m, 2H); 8.73 (s, 1H); 10.18 (s, 1H); 10.38 ppm (s, 1H). HPLC analysis on Symmetry C18 column: impurities 1.8% (column size 3.9×150 mm; mobile phase acetonitrile−0.1M phosphate buffer (pH 2.5), 28:72; sample concentration 0.25 mg/ml; detector UV 220 nm). Anal. Calcd for C16H16N2O3, %: C, 67.59; H, 5.67; N, 9.85. Found, %: C, 67.46; H, 5.61; N, 9.87.
Reaction SMILES: C([O:4][C@H:5]1[C@H:10]([O:11]C(=O)C)[C@@H:9]([CH2:15][O:16]C(=O)C)[O:8][CH:7]=[CH:6]1)(=O)C.C[O-].[Na+].CCOC(C)=O>CO>[O:8]1[C@H:9]([CH2:15][OH:16])[C@@H:10]([OH:11])[C@H:5]([OH:4])[CH:6]=[CH:7]1
Reactant: CC(=O)OC[C@H]1OC=C[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: OC[C@H]1OC=C[C@@H](O)[C@@H]1O
Reaction time: 0.33 h

Procedure:
The Tri-O-Acetyl-D-Glucal [SM-A] (100 g, 367 mmol) is dissolved in dry MeOH [1.5 L], and then NaOMe (110 mmol, 5.95 g) is added into reaction mixture. Within about 20 minutes, TLC (40% EtOAc/60% hexanes & 100% EtOAc) confirmed de-acetylated glucal. The reaction is quenched with 50WX4 cation exchange resin until pH is near 7.0 by pH strip paper. The mixture is filtered and evaporated to dryness under vacuum to yield syrupy glucal intermediate IntA1 (59 g). Theoretical yield=100 g×(146/272)=53.7 g TLC IntA1Rf=0.1, SiO2, 100% Ethyl Acetate
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N:17]1[C:30]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:24][C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2.Cl>N1C=CC=CC=1>[C:1]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N:17]1[C:30]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:24][C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Oc1ccccc1N1c2ccccc2Sc2ccccc21
Agent: Cl
Solvent: c1ccncc1
Product: O=C(Oc1ccccc1N1c2ccccc2Sc2ccccc21)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
16.0 g (114 mmol) of benzoyl chloride were added dropwise at 0-5° C. with stirring to a solution of 4.00 g (13.7 mmol) of 10-(2-hydroxyphenyl)phenothiazine in 24 ml of pyridine within 30 min. After stirring at room temperature for 2 h, the reaction solution was heated to 60-65° C. and stirred at this temperature for 15 min. After cooling to room temperature, the suspension was then stirred overnight. After adding 300 ml of ice-water, the suspension was admixed slowly with 19 ml of conc. hydrochloric acid (pH 0.9) and stirred for 1 h. The suspension was filtered through a glass frit. The residue was washed to neutrality with 2 l of water and dried at 60° C. under reduced pressure. 2.87 g (53% of theory) of colorless microcrystals having a melting point of 144-148° C. were obtained.
Reaction SMILES: C([Li])CCC.Br[C:7]1[C:8]([Cl:15])=[CH:9][C:10]([F:14])=[C:11]([CH3:13])[CH:12]=1.[C:16](=[O:18])=[O:17].O>C(OCC)C>[Cl:15][C:8]1[CH:9]=[C:10]([F:14])[C:11]([CH3:13])=[CH:12][C:7]=1[C:16]([OH:18])=[O:17]
Reactant: O=C=O
Reactant: Cc1cc(Br)c(Cl)cc1F
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: Cc1cc(C(=O)O)c(Cl)cc1F
Reaction time: 1 h

Procedure:
n-Butyllithium (1.69 M hexane solution; 14 ml) was added dropwise to a solution of 5-bromo-4-chloro-2-fluorotoluene (5.6 g) in absolute diethyl ether (100 ml) at -70° C. in a nitrogen gas stream, and the mixture was stirred at the same temperature for 1 hour. Carbon dioxide was blown into the mixture at -70° C. for 30 minutes. The temperature of the reaction mixture was given back to room temperature to conduct stirring for 2 days. Diethyl ether and water were added to the reaction mixture to conduct liquid separation. A water layer was collected, to which concentrated hydrochloric acid was added to acidify the water layer. The water layer was then Extracted with diethyl ether. An organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain the title compound (3.3 g) as a yellow solid.
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH3:20])[C:3]1=[O:21].[CH3:22][O:23][C:24]1[CH:25]=[C:26]([N:30]=[C:31]=[O:32])[CH:27]=[CH:28][CH:29]=1.C(N(CC)CC)C>C1COCC1>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([NH:30][C:31]([NH:1][CH:2]2[N:8]=[C:7]([C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=3)[C:6]3[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=3[N:4]([CH3:20])[C:3]2=[O:21])=[O:32])[CH:27]=[CH:28][CH:29]=1
Reactant: Cc1ccc(C2=NC(N)C(=O)N(C)c3ccccc32)cc1
Reactant: COc1cccc(N=C=O)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cccc(NC(=O)NC2N=C(c3ccc(C)cc3)c3ccccc3N(C)C2=O)c1
Reaction time: 0.33 h

Procedure:
Equimolar amounts of 3-(R,S)-amino-1,3-dihydro-1-methyl-5-(p-tolyl)-2H-1,4-benzodiazepin-2-one, 3-methoxyphenylisocyanate, and triethylamine were mixed in THF at 0° C. and stirred 20 minutes. Removal of THF in vacuo and crystallization from MeOH gave the title compound: m.p. 240°-242° C.
Reaction SMILES: [Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15].N1C=CN=C1>CN(C=O)C>[Cl:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCCCCCl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCCCCCl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi).