Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][CH2:12][CH2:13][OH:14].CCN(CC)CC.[CH3:22][N:23]([CH3:32])[C:24](=[O:31])[CH2:25][CH2:26][CH2:27][N+:28]([O-:30])=[O:29]>ClCCl>[CH3:32][N:23]([CH3:22])[C:24](=[O:31])[CH2:25][CH2:26][CH:27]([N+:28]([O-:30])=[O:29])[CH:13]([OH:14])[CH2:12][F:11]
Reactant: CN(C)C(=O)CCC[N+](=O)[O-]
Reactant: OCCF
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)C(=O)CCC(C(O)CF)[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 88.6 %

Procedure:
To a cooled (−78° C.) solution of oxalyl chloride (0.9 ml, 9.63 mmol) in anhydrous dichloromethane (5 ml) was added anhydrous DMSO (1.4 ml, 19.38 mmol) dropwise and the reaction mixture was stirred for 15 min. A solution of 2-fluoroethanol (0.44 mL, 7.5 mmol) in dichloromethane (2 ml) was slowly added into the reaction flask. The reaction mixture was stirred for 15 min, then it was diluted with dichloromethane (60 ml), followed by addition of dry Et3N (4.4 ml, 31.25 mmol). The reaction mixture was stirred for 15 min, then warmed to 0° C. and stirred at 0° C. for 2 h. To the reaction mixture was added a solution of N,N-dimethyl-4-nitro-butyramide (0.99 g, 6.25 mmol) in CH2Cl2 (5 ml). The reaction mixture was stirred at 0° C. for 3 h and then stirred at room temperature overnight. The mixture was concentrated and extracted with ethyl acetate. The organic layer were dried and evaporated. The residue was purified by silica gel (CH2Cl2/EtOAc=1:3) to give 1.23 g (89%) of the titled product as a colorless viscous oil. 1H NMR (CDCl3): 4.98 (bs, 1H), 4.81-4.72 (m, 1H), 4.70-4.61 (m, 1H), 4.59-4.37 (m, 1H), 4.33-4.18 (m, 1H), 3.02-2.98 (m, 3H), 2.94-2.93 (m, 3H), 2.46-2.22 (m, 4H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH:6]=[C:5]([C:8]2[CH:9]=[CH:10][C:11]([O:15][C:16]([F:19])([F:18])[F:17])=[C:12]([NH2:14])[CH:13]=2)[CH2:4][CH2:3]1>[Pd].CCO>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][C:11]([O:15][C:16]([F:17])([F:18])[F:19])=[C:12]([NH2:14])[CH:13]=2)[CH2:4][CH2:3]1
Reactant: CN1CC=C(c2ccc(OC(F)(F)F)c(N)c2)CC1
Agent: [Pd]
Solvent: CCO
Product: CN1CCC(c2ccc(OC(F)(F)F)c(N)c2)CC1
Reaction time: 6 h
Yield: 56.3 %

Procedure:
A suspension of 5-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-trifluoromethoxy-phenylamine (0.3 g, 1.10 mmol), 10% Pd/C catalyst (100 mg) in EtOH (20 mL) was hydrogenated at 40 psi for 6 hours into a Parr apparatus. The mixture was filtered over a pad of celite, the solvent removed under vacuum and the crude residue purified by flash chromatography on silica gel (eluant: DCM/MeOH/NH3 95/05/005) to yield the title compound as a light brown solid (0.17 g, 56% yield).
Reaction SMILES: C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:46]([NH2:47])=[CH:45][C:44]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:43][N:42]=2)[CH2:37][CH2:36]1.Cl[C:55]1[C:64]2[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=2[F:65])[N:58]=[C:57]([C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([CH3:73])[N:68]=2)[C:56]=1[CH3:74].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.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]>[N:38]1([C:41]2[C:46]([NH:47][C:55]3[C:64]4[C:59](=[CH:60][C:61]([F:66])=[CH:62][C:63]=4[F:65])[N:58]=[C:57]([C:67]4[CH:72]=[CH:71][CH:70]=[C:69]([CH3:73])[N:68]=4)[C:56]=3[CH3:74])=[CH:45][C:44]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:43][N:42]=2)[CH2:39][CH2:40][O:35][CH2:36][CH2:37]1
Reactant: Nc1cc(N2CCOCC2)cnc1N1CCOCC1
Reactant: Cc1cccc(-c2nc3cc(F)cc(F)c3c(Cl)c2C)n1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1cccc(-c2nc3cc(F)cc(F)c3c(Nc3cc(N4CCOCC4)cnc3N3CCOCC3)c2C)n1
Temperature: 120 °C

Procedure:
To a stirred solution of dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.025 g, 0.053 mmol), 2,5-dimorpholinopyridin-3-amine (0.104 g, 0.39 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(6-methylpyridin-2-yl)quinoline (0.10 g, 0.33 mmol) and Pd2dba3 (0.012 g, 0.013 mmol) in toluene (3.28 mL) was added sodium t-butoxide (0.079 g, 0.820 mmol). The reaction mixture was heated to 120° C. for 2 h. The reaction was then cooled to rt and diluted with water (15 mL). The mixture was extracted with EtOAc (2×15 mL) and DCM (1×15 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% hexanes/EtOAc) to give the desired product N-(2,5-di(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(6-methyl-2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 7.79 (2H, t, J=7.6 Hz), 7.58-7.72 (3H, m), 7.25 (1H, d, J=7.8 Hz), 6.97-7.07 (1H, m), 6.49 (1H, br. s.), 3.92 (4H, br. s.), 3.78-3.86 (4H, m), 3.30 (4H, br s), 3.06-3.15 (5H, m), 2.60 (3H, s), 2.18 (3H, s). Mass Spectrum (ESI) m/e=533.2 (M+1).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]2[C:8]3[S:22][C:21]([Cl:23])=[CH:20][C:9]=3[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])=[N:11][CH2:12][C:6]2=[N:5][N:4]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:30]([O:32][C:33](Cl)=[O:34])[CH3:31]>O1CCOCC1>[CH2:30]([O:32][C:33]([NH:1][CH2:2][C:3]1[N:7]2[C:8]3[S:22][C:21]([Cl:23])=[CH:20][C:9]=3[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])=[N:11][CH2:12][C:6]2=[N:5][N:4]=1)=[O:34])[CH3:31]
Reactant: CCOC(=O)Cl
Reactant: NCc1nnc2n1-c1sc(Cl)cc1C(c1ccccc1Cl)=NC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CCOC(=O)NCc1nnc2n1-c1sc(Cl)cc1C(c1ccccc1Cl)=NC2
Reaction time: 3 h

Procedure:
0.6 g of 9-aminomethyl-2-chloro-4-(o-chlorophenyl)-6H-thieno[3,2-f]-s-triazolo[4,3-a][1,4]diazepine are dissolved in 15 ml of absolute dioxane. 1.5 g of potassium carbonate are suspended in the solution and 0.18 g of chloroformic acid ethyl ester added with stirring. After 3 hours, the solid material is filtered off from the solution. The residue obtained after evaporation of the filtrate is recrystallized from ethyl acetate containing active carbon, to yield 9-ethoxycarbonylaminomethyl-2-chloro-4-(o-chlorophenyl)-6H-thieno[3,2-f]-s-triazolo[4,3-a][1,4]diazepine.
Reaction SMILES: [C:1]([O:5][C:6](=[O:40])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:39])[C:16]2[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([O:23][C:24]3[CH:29]=[CH:28][C:27]([CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:26][CH:25]=3)[CH:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:41][C:42]1[CH:43]=[C:44]([CH:47]=[C:48]([F:51])[C:49]=1F)[C:45]#[N:46]>>[C:1]([O:5][C:6](=[O:40])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:39])[C:16]2[CH:21]=[C:20]([O:22][C:49]3[C:42]([F:41])=[CH:43][C:44]([C:45]#[N:46])=[CH:47][C:48]=3[F:51])[CH:19]=[C:18]([O:23][C:24]3[CH:25]=[CH:26][C:27]([CH2:30][NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:28][CH:29]=3)[CH:17]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1ccc(Oc2cc(O)cc(C(=O)NC3CCC(NC(=O)OC(C)(C)C)CC3)c2)cc1
Reactant: N#Cc1cc(F)c(F)c(F)c1
Product: CC(C)(C)OC(=O)NCc1ccc(Oc2cc(Oc3c(F)cc(C#N)cc3F)cc(C(=O)NC3CCC(NC(=O)OC(C)(C)C)CC3)c2)cc1
Yield: 64.9 %

Procedure:
Using 0.5 g (0.89 mmol) of {4-[3-[4-tert-Butoxycarbonylaminomethylphenoxy]-5-hydroxybenzoylamino]-cyclohexyl}carbamic acid tert-butyl ester and 3,4,5-trifluoro-benzonitrile (0.34 g, 2.22 mmol) and following the procedure of Example 42(b) afforded 0.4 g of the required product. 1H NMR (DMSO-d6): δ 1.25 (4H, m), 1.38 (18H, d), 1.78 (4H, m), 3.18 (1H, m), 3.64 (1H, m), 4.12 (2H, d), 6.74 (1H, d), 6.90 (1H, s), 7.02 (2H, d), 7.20 (2H, d), 7.28 (2H, d), 7.40 (1H, m), 8.08 (2H, d), 8.32 (1H, d).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:20]([CH2:23][C:24]1[CH2:29][N:28]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26][CH:25]=1)=[N+]=[N-]>C1COCC1.O>[NH2:20][CH2:23][C:24]1[CH2:29][N:28]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26][CH:25]=1
Reactant: CC(C)(C)OC(=O)NN1CCC=C(CN=[N+]=[N-])C1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)NN1CCC=C(CN)C1
Temperature: 25 °C
Reaction time: 36 h

Procedure:
Triphenylphosphine on polystyrene (5.24 g) was added to a solution of tert-butyl 5-azidomethyl-3,6-dihydro-2H-pyridine-1-carbamate (1 g, 4.2 mmol) in THF (25 ml) and water (0.250 ml). The reaction mixture was shaken at room temperature for 36 hours. The polymer was filtered off and then washed with THF. The filtrate was concentrated.
Reaction SMILES: O[CH:2]1[C:7]([CH3:9])([CH3:8])[O:6][C:5]2[CH:10]=[CH:11][S:12][C:4]=2[CH:3]1[N:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[O:18].[K+].[Br-].[C:21]([O:24]C(=O)C)(=[O:23])[CH3:22]>Cl(O)(=O)(=O)=O>[C:21]([O:24][C:11]1[S:12][C:4]2[CH:3]([N:13]3[CH2:17][CH2:16][CH2:15][C:14]3=[O:18])[CH2:2][C:7]([CH3:9])([CH3:8])[O:6][C:5]=2[CH:10]=1)(=[O:23])[CH3:22]
Reactant: CC1(C)Oc2ccsc2C(N2CCCC2=O)C1O
Reactant: CC(=O)OC(C)=O
Agent: [Br-]
Agent: [K+]
Agent: [O-][Cl+3]([O-])([O-])O
Product: CC(=O)Oc1cc2c(s1)C(N1CCCC1=O)CC(C)(C)O2
Temperature: 0 °C

Procedure:
A solution of 5,6-dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopyrrolidin-1-yl)-7H-thieno[3,2-b]pyran (2.0 g, 7.48 mmol) and perchloric acid (70%, 10 drops) in acetic anhydride (20 mL) were stirred for 1 h at 0°-5° C. The solution was poured into ice water (100 mL). The product was extracted into dichloromethane, washed with water (4×), and evaporated in vacuo. The resultant oil was purified by flash chromatography, using 1% methanol in dichloromethane as the eluant, then crystallized from hexanes to give the product, 2.12 g (92%), as a colorless solid: mp 92°-93° C.; IR (KBr): 1745 and 1684 cm-1 ; MS: 310 (MH+); 1H NMR (CDCl3): δ1.37(s, 3H), 1.38(s, 3H), 1.98(m, 2H), 2.10(s, 3H), 2.37(m, 2H), 3.24(m, 1 H), 3.40(m, 1H), 5.15(d, J=9.1 Hz, 1H), 5.44(d, J=9.1 Hz, 1H), 6.58(d, J=5.4 Hz, 1H) and 7.13(d, J=5.4 Hz, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14]1(=[O:24])[O:19][C:17](=[O:18])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:24])[C:15]2[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([OH:19])=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=C1OC(=O)c2ccccc21
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(C(=O)c2ccccc2C(=O)O)CC1

Procedure:
A mixture of piperazine-1-carboxylic acid tert-butyl ester (167 mg, 0.90 mmol) and pthalic anhydride (160 mg, 1.08 mmol) in toluene (20 mL) were heated to reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to afford 4-(2-carboxy-benzoyl)-piperazine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=O.[Cl:10][C:11]1[CH:32]=[CH:31][CH:30]=[CH:29][C:12]=1[CH2:13][C:14]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([C:20](=[O:22])[CH3:21])[CH2:15][CH2:16][C:17]([OH:19])=[O:18].[OH-].[Na+]>C(O)C.O>[Cl:10][C:11]1[CH:32]=[CH:31][CH:30]=[CH:29][C:12]=1[CH2:13][C:14]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([C:20](=[O:22])[CH:21]=[CH:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([Cl:1])[CH:3]=1)[CH2:15][CH2:16][C:17]([OH:19])=[O:18]
Reactant: CC(=O)C(CCC(=O)O)(Cc1ccccc1Cl)c1ccccc1
Reactant: O=Cc1cccc(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)CCC(Cc1ccccc1Cl)(C(=O)C=Cc1cccc(Cl)c1)c1ccccc1
Temperature: 25 °C

Procedure:
m-Chlorobenzaldehyde (3.5 g., 0.025 mole) in ethanol (10 ml.) is added to a solution of levo-4-(o-chlorobenzyl)-4-phenyl-5-oxohexanoic acid (4.89 g., 0.015 mole) and sodium hydroxide (0.8 g., 0.02 mole) in water (50 ml.). The resulting mixture is heated on a steam bath for 24 hours. The reaction solution is cooled to room temperature, diluted with water (300 ml.), and extracted with ether to remove the excess m-chlorobenzaldehyde. Ether is expelled from the aqueous phase by warming. The solution is cooled in an ice bath, acidified with dilute hydrochloric acid (10 ml.), and the off-white solid that precipitates is filtered and air-dried. Several recrystallizations from n-butyl chloride yields 3.15 g. of material with m.p. 170°-172°C.
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([C:5]1[O:6][C:7]2[C:13]([N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)=[CH:12][CH:11]=[CH:10][C:8]=2[CH:9]=1)=[O:4].[CH:21]([C:23]1[N:28]=[CH:27][C:26]([NH:29][C:30](=[O:32])[CH3:31])=[CH:25][CH:24]=1)=[CH2:22]>>[C:30]([NH:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:21][CH2:22][N:17]2[CH2:18][CH2:19][N:14]([C:13]3[C:7]4[O:6][C:5]([C:3]([N:2]([CH3:20])[CH3:1])=[O:4])=[CH:9][C:8]=4[CH:10]=[CH:11][CH:12]=3)[CH2:15][CH2:16]2)=[N:28][CH:27]=1)(=[O:32])[CH3:31]
Reactant: C=Cc1ccc(NC(C)=O)cn1
Reactant: CN(C)C(=O)c1cc2cccc(N3CCNCC3)c2o1
Product: CC(=O)Nc1ccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)nc1

Procedure:
The compound was prepared according to the procedure disclosed in Example 43 starting from N,N-dimethyl-7-(piperazin-1-yl)benzofuran-2-carboxamide (0.075 g, 0.27 mmol) (Example 39d) and N-(6-vinylpyridin-3-yl)acetamide (0.16 g, 0.96 mmol). The product was purified by preparative HPLC to give the title compound. Yield: 0.055 g (46%).
Reaction SMILES: [CH3:1][C:2]1[CH:28]=[CH:27][C:5]([NH:6][C:7]2[CH:15]=[C:14]([C:16]([OH:18])=O)[C:13]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)=[CH:12][C:8]=2[C:9](O)=[O:10])=[CH:4][CH:3]=1.CO>O.[Fe]>[CH3:1][C:2]1[CH:28]=[CH:27][C:5]2[NH:6][C:7]3[C:8]([C:9](=[O:10])[C:4]=2[CH:3]=1)=[CH:12][C:13]1[NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][C:21]=2[C:16](=[O:18])[C:14]=1[CH:15]=3
Reactant: Cc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(C)cc3)cc2C(=O)O)cc1
Agent: [Fe]
Solvent: CO
Solvent: O
Product: Cc1ccc2[nH]c3cc4c(=O)c5cc(C)ccc5[nH]c4cc3c(=O)c2c1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
To 320 g of polyphosphoric acid (111.8% phosphoric acid) heated at 80°-95° C. was added 0.89 g (3.2 mmole) of ferrous sulfate heptahydrate followed by 72 g (0.1915 mole) of essentially iron-free 2,5-di(4-methylanilino)terephthalic acid. The iron content, relative to 2,5-di(4-methylanilino)terephthalic acid, was about 1.7 mole percent. The mixture was heated at 120°-125° C. for two hours. The viscous solution was cooled to 90°-95° C. and then slowly poured into a mixture of 470 g of methanol and 50 g of water at 40° C. The temperature of the resultant slurry was allowed to rise during the addition to about 64° C., with the temperature being controlled during addition by external cooling and adjustment of melt addition rate. The slurry was heated at reflux (68°-72° C.) for one hour, cooled to 60° C., and diluted with 600 g of water. After the slurry was stirred at 60° C. for 30 minutes, the solid component was collected by filtration and washed with water until acid-free. The resultant presscake was reslurried in 800 g of water and 33 g of 50% sodium hydroxide, then heated for 90°-95° C. for two hours. After being cooled to 70° C., the slurry was filtered and washed with water until free of alkali. The resultant presscake was reslurried in 700 g water and heated to 110°-115° C. for two hours in a closed system (e.g., a pressure reactor). After the slurry was cooled to 60°-70° C., the pH was adjusted to 3.5 with phosphoric acid and an emulsion of 2.5 g of sodium dioctyl sulfosuccinate (available as AEROSOL OT from American Cyanamid Co.), 35 g of VM&P Naphtha (available from Unocal Chemicals), and 75 g of water was added. The mixture was stirred at 30°-35° C. for three hours, collected by filtration, and washed with water. The wet cake can be oven dried or used as is for specific applications. Here, the wet cake was dried in an oven at 60° C. to give about 55 g of 2,9-dimethylquinacridone as a brilliant magenta solid. Based on a rub-out test in linseed oil (as described above), the pigment of Example 5 is significantly bluer in undertone (tint) and deeper in masstone than a comparison pigment that did not contain an iron salt in the ring closure melt or water in the drown solvent.
Reaction SMILES: [CH3:1][C:2]12[CH2:15][C:6]1([C:7]([O:9][CH2:10][C:11]([Cl:14])([Cl:13])[Cl:12])=[O:8])[N:5]1[C:16](=[O:29])[CH:17]([NH:18][C:19](=[O:28])[CH2:20][O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C@H:4]1[S:3]2.[Br-].[Al+3].[Br-].[Br-]>ClCCl>[CH3:1][CH:2]1[CH:15]=[C:6]([C:7]([O:9][CH2:10][C:11]([Cl:13])([Cl:12])[Cl:14])=[O:8])[N:5]2[C:16](=[O:29])[CH:17]([NH:18][C:19](=[O:28])[CH2:20][O:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C@H:4]2[S:3]1
Reactant: CC12CC1(C(=O)OCC(Cl)(Cl)Cl)N1C(=O)C(NC(=O)COc3ccccc3)[C@H]1S2
Agent: [Al+3]
Agent: [Br-]
Solvent: ClCCl
Product: CC1C=C(C(=O)OCC(Cl)(Cl)Cl)N2C(=O)C(NC(=O)COc3ccccc3)[C@H]2S1
Temperature: 25 °C
Reaction time: 4 h
Yield: 64.7 %

Procedure:
A solution of 2,2,2-trichloroethyl 2-methyl-2,3-methylene-6-(2-phenoxyacetamido)penam-3-carboxylate (1.39 g.) in dried dichloromethane (7 ml.) was dropwise added over 10 minutes at -10° C. to a solution of aluminum bromide (1.16 g.) in dried dichloromethane (12 ml.), and the reaction temperature was gradually elevated to room temperature, after which the mixture was stirred for 4 hours at room temperature. After the reaction, the reaction mixture was poured into ice-water (70 ml.) and the dichloromethane layer was separated, after which the aqueous layer was once extracted with chloroform. The combined dichloromethane and chloroform layer was washed in turn with water, 2% hydrochloric acid, water, a dilute sodium bicarbonate aqueous solution and water, and then dried over magnesium sulfate. After the solvent was distilled off, the obtained pale brown oil (1.2 g.) was crystallized by adding ether and a small amount of isopropyl ether. The crystals were collected by filtration, followed by washing with isopropyl ether and recrystallized from a mixture of benzene: isopropyl ether (1:3) to give colorless granules of 2,2,2-trichloroethyl 2-methyl-7-(2-phenoxyacetamido)-3-cephem-4-carboxylate (0.9 g.), mp 118° to 120° C.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:23])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH3:22])([C:14]([NH:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[O:15])[CH2:6][CH2:5]2.[O:24]=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>>[OH:24][C:7]([CH3:22])([CH2:6][CH2:5][C:4]1[C:9](=[O:8])[C:10]([CH3:13])=[C:11]([CH3:12])[C:2](=[O:1])[C:3]=1[CH3:23])[C:14]([NH:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[O:15]
Reactant: COC(=O)CNC(=O)C1(C)CCc2c(C)c(O)c(C)c(C)c2O1
Reactant: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Product: COC(=O)CNC(=O)C(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O
Yield: 81 %

Procedure:
Oxidation as described in protocol B, using 110 mg (0.344 mmol) of methyl 2-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)acetate and 415 mg CAN (0.757 mmol) yielded 94.0 mg of methyl 2-(2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamido)acetate as a yellow powder.
Reaction SMILES: [OH:1][C:2]([C:4](F)(F)F)=O.[F:8][C:9]1[CH:36]=[CH:35][C:12]([CH2:13][N:14]2[CH2:19][CH2:18][N:17]3[C:20](=[O:33])[C:21]([CH2:26][CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[C:22]([OH:25])[C:23]([OH:24])=[C:16]3[C:15]2=[O:34])=[CH:11][CH:10]=1.N1C=CC=CC=1.C(OC(=O)C)(=O)C>C(Cl)Cl>[C:2]([N:30]1[CH2:29][CH2:28][CH:27]([CH2:26][C:21]2[C:20](=[O:33])[N:17]3[CH2:18][CH2:19][N:14]([CH2:13][C:12]4[CH:11]=[CH:10][C:9]([F:8])=[CH:36][CH:35]=4)[C:15](=[O:34])[C:16]3=[C:23]([OH:24])[C:22]=2[OH:25])[CH2:32][CH2:31]1)(=[O:1])[CH3:4]
Reactant: O=C1c2c(O)c(O)c(CC3CCNCC3)c(=O)n2CCN1Cc1ccc(F)cc1
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CC(=O)N1CCC(Cc2c(O)c(O)c3n(c2=O)CCN(Cc2ccc(F)cc2)C3=O)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 2-(4-fluorobenzyl)-8,9-dihydroxy-7-(piperidin-4-ylmethyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione mono TFA salt (50 mg, 0.125 mmol) in anhydrous methylene chloride (2 mL), pyridine (12 μL, 0.149 mmol) and acetic anhydride (14 μL, 0.149 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum, and the residue was purified by prep HPLC (Gilson semi preparative HPLC system using a Waters Nova Pak column [10×40 mm I.D. cartridge, C18, 6 μM pore size) eluting with 95-5% water (0.10% TPA)/acetonitrile (0.10% TFA) gradient at 35 mL/min]. Collection and lyophilization of appropriate fractions provided he title compound as white solid.
Reaction SMILES: [CH2:1]([CH:3]1[O:5][CH2:4]1)[Cl:2].[S:6](=O)(=[O:9])([OH:8])[O-:7].[Na+:11]>>[Cl:2][CH2:1][CH:3]([OH:5])[CH2:4][S:6]([O-:9])(=[O:8])=[O:7].[Na+:11]
Reactant: O=S(=O)([O-])O
Reactant: ClCC1CO1
Agent: [Na+]
Product: O=S(=O)([O-])CC(O)CCl

Procedure:
In this example, sultaine derivatives are formed using the products of Example 2. In general, epichlorohydrin is reacted with sodium bisulfate (NaHSO3) to form sodium 3-chloro-2-hydroxypropanesulfonate. This product is then reacted with the alkylamidoalkylamine composition (e.g., from Example 2) to provide the corresponding hydroxysultaine.
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:19][CH2:20][O:21][Si](C(C)(C)C)(C)C)[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:29])[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].Cl[C:32]1[C:37]([CH3:38])=[CH:36][CH:35]=[CH:34][N:33]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:19][CH2:20][OH:21])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:29][C:32]2[C:37]([CH3:38])=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2]
Reactant: CC(=O)N1c2ccc(-c3cn(CCO[Si](C)(C)C(C)(C)C)nn3)cc2[C@H](N)C[C@@H]1C
Reactant: Cc1cccnc1Cl
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: Cc1ccccc1
Product: CC(=O)N1c2ccc(-c3cn(CCO)nn3)cc2[C@H](Nc2ncccc2C)C[C@@H]1C
Temperature: 100 °C
Reaction time: 5 h
Yield: 15 %

Procedure:
To a solution of (2S,4R)-1-acetyl-6-[1-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-1H-1,2,3-triazol-4-yl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation, see Intermediate 44) (31 mg, 0.072 mmol) and 2-chloro-3-methylpyridine (27.6 mg, 0.216 mmol) in toluene (2.5 mL) were successively added sodium tert-butoxide (69.3 mg, 0.722 mmol), tris(dibenzylideneacetone)dipalladium(0) (66.1 mg, 0.072 mmol) and 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (56.8 mg, 0.144 mmol). The resulting mixture was stirred at 100° C. for 5 h then cooled to room temperature and filtered through Celite. The insoluble material was washed with 5% MeOH in DCM. The combined filtrate and washings were concentrated in vacuo and the residue was dissolved in a 1:1 (DMSO/MeOH) mixture and purified via MDAP (modifier: formic acid). The appropriate fractions were combined and were concentrated using a blow down apparatus (45° C.) to give 2-(4-{(2S,4R)-1-acetyl-2-methyl-4-[(3-methyl-2-pyridinyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}-1H-1,2,3-triazol-1-yl)ethanol (4.5 mg, 10.63 μmol, 15%) as viscous colourless oil.