Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](Cl)=[O:8])=[CH:3][CH:2]=1.[CH3:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19].[Cl-].[Al+3].[Cl-].[Cl-]>C(=S)=S>[CH3:19][O:18][C:13]1[CH:14]=[CH:15][C:16]([C:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=2)=[O:8])=[CH:17][C:12]=1[CH3:11]
Reactant: Cc1ccc(C(=O)Cl)cc1
Reactant: COc1ccccc1C
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: COc1ccc(C(=O)c2ccc(C)cc2)cc1C

Procedure:
p-Toluoyl chloride (15.5g, 0.10 mole) is added dropwise at room temperature over a 1 hour period to a mixture of o-methylanisole (15.3 g, 0.125 mole) and aluminum chloride (AlCl3, 37.3g, 0.28 mole) in carbon disulfide (CS2, 50 ml) in a flask fitted with a stirrer, addition funnel, drying tube and reflux condenser. The reaction mixture is then refluxed for 1 hour, cooled and the carbon disulfide removed in vacuo. The residue is then slurried in methylene chloride and poured into 400 g of cracked ice containing 20 ml of concentrated hydrochloric acid. This mixture is then transferred to a separatory funnel and extracted with additional methylene chloride (3 × 15 ml) and the methylene chloride extract dried (anhydrous MgSO4) prior to concentrating in vacuo. The residue was then triturated with benzene. The benzene extract is then diluted with hexane which results in precipitation of 2.5 g. of product (10%), m.p. 73°-5°C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH:8]([CH2:14]Br)[C:9]([O:11][CH2:12][CH3:13])=[O:10].[C:16]1([C:18](=[CH:20][CH:21]=[CH:22][CH:23]=1)[OH:19])[OH:17]>CC(C)=O>[O:17]1[C:16]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[O:19][CH2:14][CH:8]1[C:9]([O:11][CH2:12][CH3:13])=[O:10]
Reactant: Oc1ccccc1O
Reactant: CCOC(=O)C(Br)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)C1COc2ccccc2O1
Yield: 80 %

Procedure:
Under a nitrogen atmosphere, add 18.2 g (131 mmol) of dry potassium carbonate and 13 g (50 mmol) of ethyl 2,3-dibromopropionate in succession to a solution of 20 g (18 1 mmol) of catechol dissolved in 120 cm3 of anhydrous acetone. The operation is repeated four times in succession at intervals of 15 minutes. The reaction mixture is heated at reflux for 18 hours, and then cooled and filtered through Celite. The filtrate is concentrated to a residual volume of 60 cm3, then hydrolysed with 80 cm3 of water and extracted with diethyl ether. After drying over magnesium sulfate, the ethereal phase is concentrated under reduced pressure and the crude product is purified by distillation under reduced pressure (b.p.=155° C. under 15 mm Hg). Ethyl 2,3-dihydro-1,4-benzodioxin-2-carboxylate is thereby obtained in a yield of 80%. nD25 =1.5214 ##STR25##
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[CH:7]=1.Cl[CH2:25][CH:26]1[O:30][C:29](=[O:31])[N:28]([CH3:32])[CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.O.C(#N)C>[CH3:32][N:28]1[CH2:27][CH:26]([CH2:25][N:10]2[CH:9]=[C:8]([C:6]3[CH:5]=[C:4]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)[CH:12]=[N:11]2)[O:30][C:29]1=[O:31]
Reactant: CN1CC(CCl)OC1=O
Reactant: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cn[nH]c2)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cnn(CC3CN(C)C(=O)O3)c2)c1
Temperature: 140 °C

Procedure:
N-[3-Methyl-5-(1H-pyrazol-4-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (100 mg, 0.31 mmol), 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (56.2 mg, 0.38 mmol), and cesium carbonate (122 mg, 0.38 mmol) were dissolved in DMA (1 mL). The mixture was then heated by microwave irradiation to 140° C. for 1.5 hours. Additional 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (30 mg, 0.19 mmol) was added and the mixture heated by microwave irradiation to 140° C. for 30 minutes. The reaction was cooled to room temperature, diluted with water (3 mL) and ACN (3 mL) then filtered through a syringe filter and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC (45 to 80% ACN/water with 0.1% TFA modifier). The free base was liberated using PL-HCO3 cartridges (Stratospheres™, 0.9 mmol) and lyophilized to afford racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one. MS ESI calcd. for C20H20F3N6O2 [M+H]+ 433. found 433. 1H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 8.80 (d, J=3.9 Hz, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 7.35 (s, 1H), 7.24 (d, J=3.4 Hz, 1H), 7.06 (s, 1H), 4.90-4.79 (m, 1H), 4.45-4.32 (m, 2H), 3.65 (t, J=8.9 Hz, 1H), 3.40 (dd, J=6.2, 9.0, 1H), 2.68 (s, 3H), 2.29 (s, 3H).
Reaction SMILES: Br[CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:3]1.[C:19]([OH:22])(=[O:21])[CH3:20]>C([O-])(=O)C.[Ag+].CO>[C:19]([O:22][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:3]1)(=[O:21])[CH3:20]
Reactant: CCOC(=O)CCCCCCC1=CC(Br)CC1=O
Reactant: CC(=O)O
Agent: [Ag+]
Agent: CC(=O)[O-]
Solvent: CO
Product: CCOC(=O)CCCCCCC1=CC(OC(C)=O)CC1=O

Procedure:
A mixture of 51.6 g. (0.137 moles) of crude 4-bromo-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g. (0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid is stirred at reflux for 4.5 hours. The mixture is cooled, and solids are removed by filtration. The filtrate is concentrated and extracted with hot hexane. The extract is washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over mangesium sulfate, and concentrated to give an oil. The crude product is distilled at reduced pressure to give a liquid, b.p. 152°-163°C. (0.01 mm); λmax.MeOH = 223 mμ (10700); νmax. = 1745 (ester carbonyl groups), 1725 (ketone carbonyl groups), and 1235 cm-1 (acetoxy group).
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[CH3:22])=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=2[CH3:14])[N:6]=1.[C:23]([Cu])#[N:24]>>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[N:6]=[C:2]([C:23]#[N:24])[S:3][C:4]=2[C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[CH3:22])=[C:8]([CH3:14])[CH:9]=1
Reactant: N#C[Cu]
Reactant: Cc1cc(Cl)ccc1-c1nc(Br)sc1-c1ccc(Cl)cc1C
Product: Cc1cc(Cl)ccc1-c1nc(C#N)sc1-c1ccc(Cl)cc1C
Temperature: 150 °C
Yield: 88.8 %

Procedure:
A round-bottomed flask was charged with 2-Bromo-4,5-bis(4-chloro-2-methylphenyl)thiazole (196 mg, 0.47 mmol) and CuCN (84.2 mg, 0.94 mmol). After degassed, 3 mL of DMF was added. The reaction mixture was heated to 150° C. overnight. After cooled to room temperature, the reaction was quenched with 25 mL of water, and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulphate and then concentrated. The residue was purified by flash chromatography to afford 150 mg of product.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[C:4](=[O:10])[NH:5][C:6](=[O:9])[NH:7][CH:8]=1.[CH2:13]([N:21]=[C:22]=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>>[CH2:13]([NH:21][C:22]([N:7]1[CH:8]=[C:3]([C:2]([F:11])([F:1])[F:12])[C:4](=[O:10])[NH:5][C:6]1=[O:9])=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: O=c1[nH]cc(C(F)(F)F)c(=O)[nH]1
Reactant: CCCCCCCCN=C=O
Product: CCCCCCCCNC(=O)n1cc(C(F)(F)F)c(=O)[nH]c1=O
Yield: 22 %

Procedure:
The title compound was obtained according to the procedure described for the synthesis of Example 1, starting from 5-(trifluoromethyl) uracil (0.10 g, 0.55 mmol); 3.0 equivalents of octyl isocyanate were used herein. The crude was purified by column chromatography using a Teledyne ISCO apparatus (gradient from cyclohexane:EtOAc 70:30 to cyclohexane:EtOAc 60:40) and then washed with n-heptane to afford the title compound (0.04 g, 22%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 0.88 (d, J=6.8 Hz, 3H), 1.18-1.44 (m, 10H), 1.53-1.70 (m, 2H), 3.41 (td, J=7.1, 5.5 Hz, 2H), 8.90-8.97 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 14.20, 22.75, 26.92, 29.20, 29.26, 31.89, 41.80, 121.16 (q, J=268.7 Hz), 139.73, 148.25, 150.83, 156.86, MS (ESI) m/z 334 [M-H]+.
Reaction SMILES: [C:1]([C:5]1[N:9]([CH3:10])[N:8]([CH2:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)[C:7](=[NH:16])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]1[CH:26]=[CH:25][C:24]([S:27](=[O:30])(=[O:29])[NH2:28])=[CH:23][C:19]=1[C:20](O)=[O:21].CCN(CC)CC.C(P(=O)(OCC)OCC)#N>C1COCC1>[NH2:28][S:27]([C:24]1[CH:25]=[CH:26][C:18]([F:17])=[C:19]([CH:23]=1)[C:20](/[N:16]=[C:7]1/[N:8]([CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15]2)[N:9]([CH3:10])[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6]/1)=[O:21])(=[O:30])=[O:29]
Reactant: NS(=O)(=O)c1ccc(F)c(C(=O)O)c1
Reactant: Cn1c(C(C)(C)C)cc(=N)n1CC1CCC1
Agent: CCOP(=O)(C#N)OCC
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cn1c(C(C)(C)C)c/c(=N\C(=O)c2cc(S(N)(=O)=O)ccc2F)n1CC1CCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 32.6 %

Procedure:
To a solution of Example 113C (0.43 g, 1.9 mmol) and 2-fluoro-5-sulfamoylbenzoic acid (Enamine, 0.47 g, 2.1 mmol) in THF (10 mL) was added Et3N (0.68 mL, 4.9 mmol) followed by diethyl cyanophosphonate (0.44 mL, 2.9 mmol). The mixture was stirred at ambient temperature for 2 hours then concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (0.26 g, 0.62 mmol, 32% yield). MS (DCI/NH3) m/z 423 (M+H)+.
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:32][CH2:31][C@@:30]2([CH3:33])[C@@H:11]([CH2:12][CH2:13][C:14]3[C:15]4[C@:26]([CH3:34])([CH2:27][CH2:28][C:29]=32)[C@@H:18]([C@H:19]([CH3:25])[CH2:20][CH2:21][C:22]([OH:24])=O)[CH2:17][CH:16]=4)[C:10]1([CH3:36])[CH3:35])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C[N:38]1[CH2:43]COCC1.[CH2:44]([O:48]C(Cl)=O)C(C)C.Cl>ClCCl>[CH3:44][O:48][N:38]([CH3:43])[C:22](=[O:24])[CH2:21][CH2:20][C@H:19]([C@@H:18]1[C@:26]2([CH3:34])[C:15]([C:14]3[CH2:13][CH2:12][C@@H:11]4[C@:30]([C:29]=3[CH2:28][CH2:27]2)([CH3:33])[CH2:31][CH2:32][C@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:10]4([CH3:36])[CH3:35])=[CH:16][CH2:17]1)[CH3:25]
Reactant: CC(C)COC(=O)Cl
Reactant: C[C@H](CCC(=O)O)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O[Si](C)(C)C(C)(C)C)C(C)(C)[C@@H]1CC3
Reactant: CN1CCOCC1
Agent: Cl
Solvent: ClCCl
Product: CON(C)C(=O)CC[C@@H](C)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O[Si](C)(C)C(C)(C)C)C(C)(C)[C@@H]1CC3
Temperature: -15 °C
Reaction time: 8 h

Procedure:
3β-tert-Butyldimethylsilyloxy-4,4-dimethyl-5α-chola-8,14-dien-24-oic acid (5.0 g) is dissolved in 250 ml of dry dichloromethane. After cooling to −15° C., 2.14 ml of N-methylmorpholine and 1.27 ml isobutylchloroformate is added and the mixture is stirred at −15° C. for 20 minutes, whereupon 0.98 g of N,O-dimethylhydroxy/amine, HCl is added and the mixture is stirred overnight and the temperature is slowly elevated to room temperature. After aqueous work-up, 3β-tert-butyldimethylsilyloxy-4,4-dimethyl-5α-chola-8,14-dien-24-oic acid-N-methoxy-N-methyl amide (5.37 g) is obtained. Melting point: 134-135° C. 1H-NMR (CDCl3, 300 MHz): δ=5.35 (1H, s); 3.69 (3H, s); 3.2 (1H, m); 3.18 (3H, s); 0.9 (9H, s); 0.04 (6H, m).
Reaction SMILES: C1([C:4](Cl)=[O:5])CC1.[Cl:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH2:13][CH2:12][C:11]2=[O:18].CN(C)[C:21]1[CH:26]=[CH:25]C=CC=1>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:25]1[CH2:26][CH2:21]1)[C:13](=[C:4]=[O:5])[CH2:12][C:11]2=[O:18]
Reactant: CN(C)c1ccccc1
Reactant: O=C(Cl)C1CC1
Reactant: O=C1CCNc2ccc(Cl)cc21
Agent: CN(C)c1ccncc1
Solvent: ClC(Cl)Cl
Product: O=C=C1CC(=O)c2cc(Cl)ccc2N1C1CC1
Reaction time: 0.17 h
Yield: 86.5 %

Procedure:
A solution of cyclopropyl-carbonyl chloride (2.09 g) in chloroform (5 ml) was added dropwise to a solution of 6-chloro-4-oxo-1,2,3,4-tetrahydroquinoline (1.815 g), N,N-dimethylaniline (2.42 g), and 4-dimethylaminopyridine (0.488 g) in chloroform (15 ml) with stirring and ice cooling over a period of 10 minutes. After being stirred overnight at ambient temperature, the mixture was washed successively with 10% hydrochloric acid, water, aqueous sodium bicarbonate, and water, dried over magnesium sulfate, and evaporated in vacuo. The residual solid was washed with diethyl ether and dried to give 6-chloro-1-cyclopropyl-carbonyl-4-oxo-1,2,3,4-tetrahydroquinoline (2.14 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([O:13][CH3:14])=[CH:7][C:4]=1[CH:5]=O.[CH2:15]([N:19]1[C:23](=[O:24])[CH2:22][NH:21][C:20]1=[O:25])[CH2:16][CH2:17][CH3:18].C(CN)O>O.C(O)C>[CH2:15]([N:19]1[C:23](=[O:24])[C:22](=[CH:5][C:4]2[CH:7]=[C:8]([O:13][CH3:14])[C:9]([O:11][CH3:12])=[CH:10][C:3]=2[O:2][CH3:1])[NH:21][C:20]1=[O:25])[CH2:16][CH2:17][CH3:18]
Reactant: COc1cc(OC)c(OC)cc1C=O
Reactant: CCCCN1C(=O)CNC1=O
Solvent: O
Solvent: NCCO
Solvent: CCO
Product: CCCCN1C(=O)NC(=Cc2cc(OC)c(OC)cc2OC)C1=O
Yield: 86.7 %

Procedure:
A mixture of 2,4,5-trimethoxybenzaldehyde (9.8 g; 0.05 mole), 3-n-butylhydantoin (7.8 g: 0.05 mole) and ethanolamine (4.6 g; 0.075 mole) in water/ethanol (50 ml/30 ml) was stirred and boiled under reflux for 3 hours. The cloudy solution was cooled in the refrigerator and the resultant yellow solid filtered off, washed with water, sucked dry and recrystallised from ethanol to give the title compound (14.5 g; 87%) m.p. 170° C.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]([OH:17])=O)=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.[NH2:20][CH:21]1[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:23][CH2:22]1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH2:27]([N:24]1[CH2:25][CH2:26][CH:21]([NH:20][C:15]([C:10]2[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:8][CH:7]=3)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:17])[CH2:22][CH2:23]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: O=C(O)c1ccccc1-c1ccc(C(F)(F)F)cc1
Reactant: NC1CCN(Cc2ccccc2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NC1CCN(Cc2ccccc2)CC1)c1ccccc1-c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.7 %

Procedure:
4′-Trifluoromethyl-biphenyl-carboxylic acid (5.0 g) was dissolved in dimethylformamide (50 mL), and to this solution were added at room temperature 4-amino-1-benzylpiperidine (3.55 g), 1-hydroxybenzotriazole hydrate (3.0 g) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (3.58 g). The mixture was stirred at room temperature overnight, and the reaction solution was concentrated in vacuo to precipitate crystals. The crystals were washed successively with saturated aqueous sodium bicarbonate and water, and dried in vacuo to give the title compound (7.42 g).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C@H:11]2[CH2:13][C@@H:12]2[CH2:14][OH:15])=[N:9][CH:10]=1.[Br:16][C:17]1[C:18](Cl)=[N:19][C:20](Cl)=[N:21][CH:22]=1.[CH2:25]1COCC1>>[Br:16][C:17]1[C:18]([O:15][CH2:14][C@H:12]2[CH2:13][C@@H:11]2[C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:10][N:9]=2)=[N:19][C:20]([CH3:25])=[N:21][CH:22]=1
Reactant: C1CCOC1
Reactant: Clc1ncc(Br)c(Cl)n1
Reactant: COc1ccc([C@H]2C[C@@H]2CO)nc1
Agent: [H-]
Agent: [Na+]
Product: COc1ccc([C@H]2C[C@@H]2COc2nc(C)ncc2Br)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
NaH (78 mg, 1.95 mmol, 60% disp.) was added to a stirring solution of [(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methanol (S,S-DD3, ent2) (350 mg, 1.953 mmol) and 5-bromo-2,4-dichloropyrimidine (445 mg, 1.953 mmol) in THF (9.77 mL). The reaction mixture was stirred at room temperature for 1 hour, and then quenched by dropwise addition of saturated aqueous NaHCO3. The reaction mixture was diluted with EtOAc (50 mL), and washed with saturated aqueous NaHCO3 (50 mL) and brine (50 mL). The organics were dried over MgSO4, filtered, and concentrated in vacuo to afford the title compound as an orange gum. The unpurified product was sufficiently pure to use in the subsequent step without further purification. LRMS m/z (M+H) 372.2 found, 372.0 required.
Reaction SMILES: CS(C)=O.[OH-:5].[K+].[OH2:7].C1(C2[C:21]3[C:20](=O)[N:19]=[C:18]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:17]=3[C:16](=O)[N:15]=2)C=CC=CC=1>CO>[CH:27]1[CH:28]=[C:23]2[C:18]([C:17]3[C:20]([NH:19][C:24]2=[CH:25][CH:26]=1)=[CH:21][C:17]1[C:18]([C:23]2[C:28]([NH:15][C:16]=1[CH:16]=3)=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:7])=[O:5]
Reactant: O
Reactant: O=c1nc(-c2ccccc2)c2c(=O)nc(-c3ccccc3)c1=2
Reactant: [OH-]
Agent: [K+]
Solvent: CO
Solvent: CS(C)=O
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Reaction time: 0.08 h

Procedure:
A 500 ml flask equipped with a stirrer, thermometer, and condenser is charged with 100 ml DMSO, 8.9 grams of 45% aqueous potassium hydroxide, and 9 ml water. 8.5 grams unsubstituted gamma-II-quinacridone and 1.5 grams 3,6-diphenyl-1,4-diketopyrrolo[3,4-c]pyrrole are added at 40°-50° C. The mixture is heated and stirred for 5 minutes at 80°-90° C. The resulting deep blue solution of the pigment salts is drowned into methanol at 20°-40° C., causing the pigment to precipitate. The pigment suspension is stirred at reflux temperature for 1 hour, then filtered. The presscake is washed DMSO-free with methanol, followed by water to a pH 7.0-8.0, and then dried. The pulverized pigment shows the x-ray diffraction pattern of a gamma-1-quinacridone without peaks of the DPP pigment and different from the x-ray diffraction diagram of the gamma-II-quinacridone starting material. Thus, a quinacridone/DPP pigment solid solution with the quinacridone as host is formed. The pigment solid solution shows an opaque highly saturated strong red color when applied in plastics or paints with excellent weatherfastness properties.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.[H-].[Na+].F[C:11]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][CH:14]=[CH:13][N:12]=1.O>C1COCC1>[N+:17]([C:16]1[C:11]([O:7][CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[N:12][CH:13]=[CH:14][CH:15]=1)([O-:19])=[O:18]
Reactant: O=[N+]([O-])c1cccnc1F
Reactant: OC1CCOCC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cccnc1OC1CCOCC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 51.3 %

Procedure:
To a stirred solution of tetrahydro-2H-pyran-4-ol (2.5 g, 24.5 mmol) in anhydrous THF (20 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 0.938 g, 24.5 mmol) and the mixture stirred at 0° C. for 0.5 h. A solution of 2-fluoro-3-nitro-pyridine (3.3 g, 23.2 mmol) in anhydrous THF (5 mL) was added drop wise with stirring and the solution allowed to warm to ambient temperature over 5 hours. The reaction was cooled in an ice-bath and water (50 mL) added. The mixture was extracted with EtOAc (2×100 mL) and the combined organic layers washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified flash column chromatography (20% iso-hexane/DCM DCM) to yield the title compound as pale yellow oil (2.67 g, 48% yield).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH:20]([CH3:22])[CH3:21].Cl>CN(C=O)C>[CH3:21][CH:20]([O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=1)[CH3:22]
Reactant: COC(=O)Cc1ccc(O)cc1
Reactant: CC(C)Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)Cc1ccc(OC(C)C)cc1
Reaction time: 8 h

Procedure:
Methyl (4-hydroxyphenyl)acetate (1.0 g, 1.0 eq), Cs2CO3 (2.15 g, 1.1 eq) and 2-bromopropane (0.565 mL. 1.0 eq) were combined in 100 ml DMF at room temperature. The mixture was stirred overnight. The suspension was poured into 50 mL 1 N HCl and extracted with ethyl acetate. The organic phase was separated and washed with water followed by sodium bicarbonate. The organic phase was dried over sodium sulfate and the solvent was evaporated to give an oil. The resulting oil was chromatographed on silica gel using hexanes and ethyl acetate (95:5) to give methyl (4-(1-methylethoxy)phenyl)acetate.
Reaction SMILES: [ClH:1].[Cl:2][CH2:3][CH2:4][C:5]1([CH3:18])[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]2[CH:14]=[CH:15][CH:16]=[N:17][C:7]=2[O:6]1.[CH3:19][NH:20][CH3:21]>CO>[ClH:2].[ClH:1].[CH3:19][N:20]([CH3:21])[CH2:3][CH2:4][C:5]1([CH3:18])[CH2:11][N:10]([CH3:12])[C:9](=[O:13])[C:8]2[CH:14]=[CH:15][CH:16]=[N:17][C:7]=2[O:6]1
Reactant: CN1CC(C)(CCCl)Oc2ncccc2C1=O
Reactant: CNC
Agent: Cl
Solvent: CO
Product: CN(C)CCC1(C)CN(C)C(=O)c2cccnc2O1
Reaction time: 192 h
Yield: 67 %

Procedure:
To 4.5 g (0.015 mole) of 2-(2-chloroethyl)-2,3-dihydro-2,4-dimethylpyrido[3,2-f]-1,4-oxazepin-5(4H)-one hydrochloride in 15 ml of methanol was added 40 ml of dimethylamine. The flask was sealed tightly and left standing at room temperature for 8 days. The methanol and dimethylamine were removed by rotary evaporation (70° C.; 30 mm). The residue was taken up in 150 ml of chloroform, washed with 2×50 ml dil aqueous sodium hydroxide, dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation (70° C.; 30 mm). The syrupy residue was treated with hydrogen chloride in isopropyl alcohol, which afforded 3.5 g (67%) of white crystals, m.p. 188°-90° C.
Reaction SMILES: [SH:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[CH2:7](O[K])C.ClC[CH:13]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:14][Si:15]([O:20][CH3:21])([O:18][CH3:19])[O:16][CH3:17]>C(O)C>[CH3:21][O:20][Si:15]([O:16][CH3:17])([O:18][CH3:19])[CH2:14][CH2:13][C:22]1[CH:23]=[CH:24][C:25]([CH2:7][S:1][C:2]2[N:6]=[CH:5][NH:4][N:3]=2)=[CH:26][CH:27]=1
Reactant: Sc1nc[nH]n1
Reactant: CO[Si](CC(CCl)c1ccccc1)(OC)OC
Reactant: CCO[K]
Solvent: CCO
Product: CO[Si](CCc1ccc(CSc2nc[nH]n2)cc1)(OC)OC
Reaction time: 0.08 h
Yield: 53 %

Procedure:
10 mmole of 3-mercapto-1H-1,2,4-triazole was dissolved in 20 ml ethanol, then 10 mmole EtOK was added, and stirred for 5 minutes. 10 mmole of ((chloromethyl)phenylethyl)trimethoxysilane was added to the solution, and stirred for 6 hours. The white precipitate was removed by filtration, the solvent in the filtrate was removed in vacuum. The obtained solid was dissolved in methanol, and separated with a Si gel column (solvents: 7 ethylacetate/3 hexane in volume). Yield: 53%. 1H NMR (CDCl3) of Precursors 6: δ(ppm) 8.09 (1H, s), 7.19 (4H, m), 4.29 (2H, s), 3.55 (9H, s), 2.72 (2H, t, JH-H=8.50), 1.02 (2H, t, JH-H=8.50).