Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:15]([O:19][C:20]([N:22]1[CH2:26][C@@H:25]([O:27][C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=2)[CH2:24][C@H:23]1[CH2:38][OH:39])=[O:21])([CH3:18])([CH3:17])[CH3:16].O[C:41]1[CH:50]=[CH:49][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:43][CH:42]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:26][C@@H:25]([O:27][C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=2)[CH2:24][C@H:23]1[CH2:38][O:39][C:41]1[CH:50]=[CH:49][C:44]([C:45]([O:47][CH3:48])=[O:46])=[CH:43][CH:42]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](Oc2ccc3ccccc3c2)C[C@H]1CO
Reactant: COC(=O)c1ccc(O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OC[C@@H]2C[C@H](Oc3ccc4ccccc4c3)CN2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Yield: 93.4 %

Procedure:
DIAD (0.37 ml, 1.86 mmol) was added to a solution of (2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethanol (640 mg, 1.86 mmol), methyl 4-hydroxybenzoate (283 mg, 1.86 mmol) and triphenylphosphine (488 mg, 1.86 mmol) in THF (18 ml) under stirring at room temperature in a nitrogen gas stream. The reaction mixture was stirred overnight at room temperature. The residue obtained by concentrating the reaction mixture under reduced pressure was purified by chromatography on a silica gel column (silica gel: 100 g), whereby from hexane/ethyl acetate (2/1) eluate fractions, the title compound (830 mg, 93%) was obtained as a colorless oil.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:18]=[C:17]([C:28]([N:30]([O:32][CH3:33])[CH3:31])=[O:29])[CH:16]=2)=[CH:11][CH:10]=1.CCN(CC)CC>C(Cl)Cl.C(Cl)(Cl)Cl>[CH3:1][S:2]([O:6][CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:18]=[C:17]([C:28]([N:30]([O:32][CH3:33])[CH3:31])=[O:29])[CH:16]=2)=[CH:13][CH:14]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(-n2nc(C(=O)N(C)OC)cc2-c2ccc(CCO)cc2)cc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(-n2nc(C(=O)N(C)OC)cc2-c2ccc(CCOS(C)(=O)=O)cc2)cc1
Reaction time: 1 h
Yield: 99.8 %

Procedure:
A solution of methanesulfonyl chloride (328 mg) in CH2Cl2 (2 ml) was added to a solution of 5-[4-(2-hydroxyethyl)-phenyl]-N-methoxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-carboxamide (840 mg) and Et3N (334 mg) in CH2Cl2 (10 ml) under ice bath cooling. The mixture was stirred at same temperature for 1 hour. The mixture was diluted with CHCl3 and washed with 1M HCl, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt/n-hexane=80%, 90%. The pure fractions were collected and concentrated in vacuo to give 2-{4-[3-{[methoxy(methyl)amino]carbonyl}-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}ethyl methanesulfonate (1.01 g) as an oil.
Reaction SMILES: Cl.[NH2:2][C@@H:3]1[C:12]([CH3:14])([CH3:13])[C:11]2[CH:10]=[C:9]([C:15]([NH2:17])=[O:16])[CH:8]=[CH:7][C:6]=2[CH2:5][C@H:4]1[O:18][CH3:19].C(N(CC)C(C)C)(C)C.[CH:29]([C@@H:31]1[CH2:35]OC(C)(C)[N:32]1C(OCCCC)=O)=[O:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.CO.CC(O)=O>[NH2:32][C@@H:31]([CH2:29][OH:30])[CH2:35][NH:2][C@@H:3]1[C:12]([CH3:14])([CH3:13])[C:11]2[CH:10]=[C:9]([C:15]([NH2:17])=[O:16])[CH:8]=[CH:7][C:6]=2[CH2:5][C@H:4]1[O:18][CH3:19]
Reactant: CCCCOC(=O)N1[C@H](C=O)COC1(C)C
Reactant: CO[C@@H]1Cc2ccc(C(N)=O)cc2C(C)(C)[C@H]1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Solvent: CC(=O)O
Product: CO[C@@H]1Cc2ccc(C(N)=O)cc2C(C)(C)[C@H]1NC[C@@H](N)CO
Reaction time: 1 h
Yield: 118.2 %

Procedure:
To a suspension of trans-7-amino-6-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid amide hydrochloride (229.3 mg, 0.81 mmol) in a mixture of dichloromethane (2.0 mL) and methanol (0.3 mL) was added N,N-diisopropyl-ethylamine (0.10 g, 0.80 mmol) followed by tort-butyl (4S)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (0.18 g, 0.80 mmol). Sodium triacetoxyborohydride (0.20 g, 0.97 mmol) was added and the reaction mixture was stirred for 1 h. The reaction mixture was concentrated to dryness and dissolved in ethyl acetate (40 mL). The suspension was washed with saturated sodium bicarbonate (15 mL) and brine (15 mL), dried over sodium sulfate, filtered and concentrated to give a white foam. The white foam was treated with AcOH (1.0 mL) and 6N HCl (1.0 mL) at 70° C. for 1 h. The reaction mixture was concentrated, and evaporated with ethyl acetate (3×2 mL) to give the hydrochloride salt of the title compound as a dark greenish powder (304 mg, 96% yield). (m/z): [M+H]+ calcd for C17H27N3O3, 322.21; found, 322.2.
Reaction SMILES: [C:1]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].C(N(CC)CC)C.[Br-].[C:22]([O:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][N+:33]([CH2:36][C:37]([C:39]2[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[C:41]([O:48][CH3:49])[CH:40]=2)=[O:38])=[CH:32][CH:31]=1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>CN(C)C=O.[O-2].[Mn+2]>[C:22]([O:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][N:33]2[C:32]([CH:31]=1)=[C:2]([C:1]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5])[C:3]([CH3:4])=[C:36]2[C:37](=[O:38])[C:39]1[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[C:41]([O:48][CH3:49])[CH:40]=1)=[O:28])([CH3:25])([CH3:24])[CH3:23]
Reactant: C/C=C/C(=O)OCc1ccccc1
Reactant: COc1cc(C(=O)C[n+]2ccc(NC(=O)OC(C)(C)C)cc2)ccc1[N+](=O)[O-]
Agent: [Mn+2]
Agent: [Br-]
Agent: [O-2]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(C(=O)c2c(C)c(C(=O)OCc3ccccc3)c3cc(NC(=O)OC(C)(C)C)ccn23)ccc1[N+](=O)[O-]
Temperature: 90 °C
Yield: 43.5 %

Procedure:
9.4 g (53.38 mmol) of benzyl crotonate, 1.8 mL (12.8 mmol) of triethylamine and 3.7 g (42.68 mmol) of manganese oxide are successively added to a solution of 5.0 g (10.67 mmol) of 4-[N-(tert-butoxycarbonyl)amino]-1-[2-(3-methoxy-4-nitrophenyl)-2-oxoethyl]pyridinium bromide in 40 mL of dimethylformamide. The reaction mixture is then heated at 90° C. for 4 hours and then filtered on a silica bed, eluting with ethyl acetate. The filtrate is poured over water and extracted with ethyl acetate. After decantation, the organic phase is washed with a saturated sodium chloride solution, dried over sodium sulfate and then concentrated under reduced pressure. The product is purified by chromatography on silica gel, eluting with a toluene/ethyl acetate (95/5 to 70/30) mixture. 2.6 g of an orange-coloured powder are obtained.
Reaction SMILES: Cl[CH2:2][C:3]1[S:4][C:5]([CH:8]2[CH2:10][CH2:9]2)=[N:6][N:7]=1.[CH:11]([N:14]1[CH2:19][CH2:18][CH:17]([NH:20][S:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]2[S:30][C:31]([Cl:34])=[CH:32][CH:33]=2)=[O:28])(=[O:23])=[O:22])[CH2:16][CH2:15]1)([CH3:13])[CH3:12]>>[CH:8]1([C:5]2[S:4][C:3]([CH2:2][N:20]([CH:17]3[CH2:18][CH2:19][N:14]([CH:11]([CH3:13])[CH3:12])[CH2:15][CH2:16]3)[S:21]([CH2:24][CH2:25][NH:26][C:27]([C:29]3[S:30][C:31]([Cl:34])=[CH:32][CH:33]=3)=[O:28])(=[O:22])=[O:23])=[N:7][N:6]=2)[CH2:10][CH2:9]1
Reactant: CC(C)N1CCC(NS(=O)(=O)CCNC(=O)c2ccc(Cl)s2)CC1
Reactant: ClCc1nnc(C2CC2)s1
Product: CC(C)N1CCC(N(Cc2nnc(C3CC3)s2)S(=O)(=O)CCNC(=O)c2ccc(Cl)s2)CC1

Procedure:
5-Chloro-thiophene-2-carboxylic acid {2-[(5-cyclopropyl-[1,3,4]thiadiazol-2-ylmethyl)-(1-isopropyl-piperidin-4-yl)-sulfamoyl]-ethyl}-amide was prepared by an analogous procedure as described in example 15 starting from 89 mg (2 equiv.) 2-chloromethyl-5-cyclopropyl-[1,3,4]thiadiazole and 100 mg (0.25 mmol) 5-chloro-thiophene-2-carboxylic acid [2-(1-isopropyl-piperidin-4-ylsulfamoyl)-ethyl]-amide. Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.1% TFA) gave pure 5-chloro-thiophene-2-carboxylic acid {2-[(5-cyclopropyl-[1,3,4]thiadiazol-2-ylmethyl)-(1-isopropyl-piperidin-4-yl)-sulfamoyl]-ethyl}-amide. The title compound was obtained as its trifluoroacetate in form of a colorless amorphous material.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].CC([O-])(C)C.[K+].CN1CCCC1=O.[Cl:25][C:26]1[CH:31]=[C:30](F)[CH:29]=[CH:28][N:27]=1>CCOC(C)=O>[Cl:25][C:26]1[CH:31]=[C:30]([O:8][C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=2)[CH:29]=[CH:28][N:27]=1
Reactant: Cc1ccc(O)cc1[N+](=O)[O-]
Reactant: Fc1ccnc(Cl)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Cc1ccc(Oc2ccnc(Cl)c2)cc1[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 57.9 %

Procedure:
Add 4-methyl-3-nitrophenol (6.95 g, 45.46 mmol) and t-BuOK (5.94 g, 53.03 mmol) to N-methylpyrrolidin-2-one (100 mL), stir for 30 min, then add 2-chloro-4-fluoro-pyridine (5 g, 37.88 mmol) and stir the reaction at 70° C. overnight. TLC (PE:EtOAc=3:1) shows the reaction is complete. Add water (250 mL) to the reaction mixture, extract with EtOAc (100 mL×4), combine the organic layers, wash with water, brine respectively and dry over Na2SO4. Concentrate to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=1:4) affords the title compound (5.8 g, 58%). MS: (M+1): 265.1.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5](I)[CH:4]=[C:3]1[C:8]([O:10][CH3:11])=[O:9].[CH3:12][C:13]1([CH3:32])[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[C:23]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][C:19](B(O)O)=[CH:20]3)=[CH:15][C:14]1=2.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH:6]=[C:5]([C:19]2[CH:18]=[CH:17][C:16]3[C:21](=[CH:22][C:23]4[C:24]([CH3:28])([CH3:27])[CH2:25][CH2:26][C:13]([CH3:32])([CH3:12])[C:14]=4[CH:15]=3)[CH:20]=2)[CH:4]=[C:3]1[C:8]([O:10][CH3:11])=[O:9]
Reactant: CC1(C)CCC(C)(C)c2cc3cc(B(O)O)ccc3cc21
Reactant: COC(=O)c1cc(I)cn1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: COC(=O)c1cc(-c2ccc3cc4c(cc3c2)C(C)(C)CCC4(C)C)cn1C
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 33.9 %

Procedure:
231 mg (0.2 mml) of tetrakis-(triphenylphosphine)palladium (0), 50 ml of toluene and 1.75 g (6.6 mmol) of methyl N-methyl-4-iodo-2-pyrrolecarboxylate were introduced into a three-necked flask and under a nitrogen stream and the mixture was stirred at room temperature for 20 minutes. 2.8 g (10 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthrylboronic acid and 6.6 ml of an aqueous potassium carbonate solution (2N) were then added and the mixture was heated at reflux for 8 hours. The reaction medium was evaporated to dryness, taken up in water and ethyl ether, the organic phase decanted, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on a silica column eluted with a mixture of dichloromethane and hexane (80/20). 840 mg (47%) of methyl N-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthryl)-2-pyrrolecarboxylate were obtained.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]1([C:13]2[N:14]=[C:15]3[C:20]([CH2:21][OH:22])=[CH:19][CH:18]=[CH:17][N:16]3[CH:23]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.O>C(Cl)Cl.CS(C)=O>[CH:21]([C:20]1[C:15]2[N:16]([CH:23]=[C:13]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:14]=2)[CH:17]=[CH:18][CH:19]=1)=[O:22]
Reactant: OCc1cccn2cc(-c3ccccc3)nc12
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: O=Cc1cccn2cc(-c3ccccc3)nc12
Yield: 84.8 %

Procedure:
A mixture of 14.8 ml of dimethyl sulphoxide and 45 ml of methylene chloride is added dropwise to 8.7 ml (110 mmol) of oxalyl chloride in 220 ml of methylene chloride at -60° C. under inert conditions. 19.5 g (87 mmol) of 2-phenyl-8-hydroxymethyl-imidazo[1,2-a]pyridine in 90 ml of methylene chloride and 45ml of dimethyl sulphoxide are then added dropwise at -60° C., while stirring, and the mixture is stirred at -60° C. for 15 minutes end at -10° C. for 1 hour. 60.9 ml of triethylamine are now added and the mixture is stirred at -10° C. for 5 minutes and then allowed to come to room temperature. For working up, water is added, the organic phase is separated off and the aqueous phase is extracted twice more with methylene chloride. The combined organic phases are washed with saturated NaCl solution, dried over Na2SO4 and concentrated on a rotary evaporator. Stirring of the residue with ether gives 16.4 g of crystals (=73.8% of theory), which are chromatographed over silica gel for removal of chlorinated by-products.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]([OH:14])=O.[CH3:15][CH:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17]1>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]([N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:24][CH2:25][CH:16]1[CH3:15])=[O:14]
Reactant: O=C(O)CSc1nc2ccccc2s1
Reactant: CC1CCc2ccccc2N1
Product: CC1CCc2ccccc2N1C(=O)CSc1nc2ccccc2s1
Yield: 40 %

Procedure:
The title compound was synthesized according to General Procedure B using 2-(benzo[d]thiazol-2-ylthio)acetic acid and 2-methyl-1,2,3,4-tetrahydroquinoline to yield 40 as a pale yellow solid (0.32 g, 40%); MS m/z: 355 (M+H)+. Anal. Calcd. For, C19H18N2OS2: C, 64.38; H, 5.12; N, 7.90; S, 18.09. Found: C, 64.38; H, 5.22; N, 7.85; S, 17.93.
Reaction SMILES: [Br:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C@@H:11]([OH:13])[CH3:12])[C:5]=2[O:4][C:3]=1[CH3:14].N1C=CN=C1.[CH3:20][C:21]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C(Cl)Cl>[Br:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C@@H:11]([O:13][Si:24]([C:21]([CH3:23])([CH3:22])[CH3:20])([CH3:26])[CH3:25])[CH3:12])[C:5]=2[O:4][C:3]=1[CH3:14]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Cc1oc2c([C@H](C)O)cccc2c1Br
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: Cc1oc2c([C@H](C)O[Si](C)(C)C(C)(C)C)cccc2c1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 94.9 %

Procedure:
A solution of (S)-1-(3-bromo-2-methyl-benzofuran-7-yl)-ethanol (1.39 g, 5.47 mmol) in CH2Cl2 (50 mL) is treated with imidazol (0.56 g, 8.21 mmol) and TBSCl (0.91 g, 6.02 mmol). The reaction is stirred at rt overnight. It is diluted with CH2Cl2 (50 mL); washed with 0.1 M HCl (3×30 mL); dried with Na2SO4; filtered and concentrated. The resulting crude material is purified by chromatography gives the title compound (1.92 g, 5.19 mmol, 95%). 1H NMR (CDCl3): δ. −0.02 (s, 3H), 0.07 (s, 3H), 0.91 (s, 3H), 2.48 (s, 3H), 1.52 (d, J=6.2 Hz, 3H), 5.38 (q, J=6.2 Hz, 1H), 7.25 (t, J=8.0 Hz, 1H), 7.30 (dd, J=8.0, 1.7 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H) ppm.
Reaction SMILES: [CH:1]1([C:6](=[O:18])[CH2:7][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[C:11]=2O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.S(=O)(=O)(O)O.O>C(O)(=O)C>[CH:1]1([C:6]2[O:18][C:11]3[C:12]([CH3:16])=[CH:13][CH:14]=[CH:15][C:10]=3[C:8](=[O:9])[CH:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Cc1cccc(C(=O)CC(=O)C2CCCC2)c1O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: Cc1cccc2c(=O)cc(C3CCCC3)oc12
Temperature: 100 °C
Reaction time: 1 h
Yield: 97.9 %

Procedure:
1-Cyclopentyl-3-(2-hydroxy-3-methylphenyl)-1,3-propanedione (14 g) was dissolved in acetic acid (70 ml) and conc. sulfuric acid (3 ml) was added to the solution. The mixture was stirred at 100° C. for 1 hour. The reaction mixture was poured into cold water and extracted with ethyl acetate. The extract was washed with water, aqueous saturated sodium bicarbonate and then water and dried (MgSO4). The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate (4:1)) to obtain the title compound (12.7 g) as crystals, yield 97.4%. The crystals were recrystallized from methanol to obtain prisms, m.p. 51°-52° C.
Reaction SMILES: [CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]([CH:16]=[CH:17][CH:18]=1)[NH2:15].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1[C:6]([C:12]2[CH:13]=[C:14]([NH2:15])[CH:16]=[CH:17][CH:18]=2)=[C:5]([CH3:10])[O:4][N:3]=1
Reactant: Cc1noc(C)c1B(O)O
Reactant: Nc1cccc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Cc1noc(C)c1-c1cccc(N)c1
Temperature: 25 °C
Yield: 71 %

Procedure:
3,5-dimethylisoxazole-4-boronic acid (0.123 g, 0.872 mmol) and 3-bromoaniline (0.063 mL, 0.581 mmol) were combined in DME (2 mL) in a flame-dried, round-bottom flask. Na2CO3 (2M, 0.610 mL, 1.22 mmol) and Pd(PPh3)4 (0.02 g, 0.017 mmol) were added to the stirred solution. The reaction was refluxed overnight under argon flow, and subsequently cooled to room temperature. The solvent was removed under vacuum and the resulting residue was resuspended in CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated under vacuum. The crude product was purified by flash silica column chromatography (10-60% EtOAc/hexanes). The purification was monitored by TLC. The solvent was removed under vacuum from fractions containing product, resulting in 0.077 g in 71% yield.
Reaction SMILES: C1(CCCCOCCCCCCBr)C=CC=CC=1.C1(=O)NC(=O)C2=CC=CC=C12.[K].[C:31]1([CH2:37][CH2:38][CH2:39][CH2:40][O:41][C:42]2[CH:43]=[CH:44][CH:45]=[C:46]3[C:51](=O)[N:50](CCCCCC)C(=O)C=23)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN>CC(C)=O.ClCCl>[C:31]1([CH2:37][CH2:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:51][NH2:50])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CCCCCCN1C(=O)c2cccc(OCCCCc3ccccc3)c2C1=O
Agent: BrCCCCCCOCCCCc1ccccc1
Agent: CN
Agent: O=C1NC(=O)c2ccccc21
Solvent: CC(C)=O
Solvent: ClCCl
Product: NCCCCCCOCCCCc1ccccc1

Procedure:
A solution of 46.6 g (0.15 mol) of 6-(4-phenylbutoxy)-hexyl-bromide and 27.6 g (0.15 mol) of potassium phthalimide in 400 ml of acetone is refluxed for 70 hours. After cooling, the potassium bromide precipitated is removed by suction filtering and the solvent is distilled off in vacuo. The oily residue thus obtained, consisting of crude 6-(4-phenyl-butoxy)-N-hexyl-phthalimide, is stirred into 300 ml of dichloromethane and 300 ml of 40% methylamine solution overnight. The organic phase is separated off and the aqueous phase is extracted twice more with dichloromethane. The combined organic phases are dried over sodium sulphate and evaporated down in vacuo. The oily residue is dissolved in ether, the solids precipitated are filtered off and the filtrate is evaporated to dryness. The colorless oil remaining is distilled. Bp0.2 =143°-145° C.
Reaction SMILES: OS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[Cl:20][C:21]1[CH:22]=[C:23]([C:27]([CH3:43])([CH2:41][CH3:42])[C:28]([CH:30]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:31](OCC)=[O:32])=[O:29])[CH:24]=[CH:25][CH:26]=1>>[Cl:20][C:21]1[CH:22]=[C:23]2[C:24]([C:31]([OH:32])=[C:30]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:28](=[O:29])[C:27]2([CH2:41][CH3:42])[CH3:43])=[CH:25][CH:26]=1
Reactant: CCOC(=O)C(C(=O)OCC)C(=O)C(C)(CC)c1cccc(Cl)c1
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Agent: O=S(=O)(O)O
Product: CCOC(=O)C1=C(O)c2ccc(Cl)cc2C(C)(CC)C1=O
Reaction time: 1.5 h
Yield: 46.5 %

Procedure:
H2SO4 (40 mL, 473 mmol) was cooled to 0° C. and treated with P2O5 (15 g, 106 mmol). The mixture was brought to room temperature and added to diethyl 2-(2-(3-chlorophenyl)-2-methylbutanoyl)malonate (7.67 g, 22 mmol). The reaction mixture was then stirred for 1.5 hours. Ice (H2O) was added, and the aqueous mixture was extracted with EtOAc (3×). The combined organic layers were washed with water (2×) and brine, dried (MgSO4), and concentrated in vacuo to give the crude compound as an orange oil. The crude oil was purified by silica flash chromatography (0-100% DCM/hexane) to give the desired compound as a yellow solid (3.16 g). MS (m/e)=309.1 (M+H)+.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7].C(=O)([O-])[O-].[K+].[K+].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16]>CC(C)=O.CCOC(C)=O>[CH3:14][Si:15]([CH3:17])([CH3:16])[CH2:18][CH2:19][O:20][CH2:21][N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]=[O:7]
Reactant: O=Cc1ncc[nH]1
Reactant: C[Si](C)(C)CCOCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: C[Si](C)(C)CCOCn1ccnc1C=O
Temperature: 60 °C
Yield: 60.2 %

Procedure:
A mixture of 1H-imidazole-2-carbaldehyde (1.1 g, 11 mmol), potassium carbonate (3.0 g, 23 mmol), and SEM-Cl (2.4 mL, 14 mmol) in 10 mL of acetone was heated to 60° C. for 8 h. The mixture was diluted with EtOAc (100 mL) and washed with NaHCO3 (2×100 mL) and brine (100 mL) and the organic layer dried (Na2SO4) and concentrated. The title compound was purified by elution from a 20-g SPE column with 50% EtOAc to give 1.5 g (58%) of a colorless oil. 1H-NMR (CDCl3, 400 MHz): δ 9.82 (s, 1H), 7.38 (d, J=1.0 Hz, 1H), 7.34 (d, J=1.0 Hz, 1H), 5.78 (s, 2H), 3.55 (m, 2H), 0.94 (m, 2H), −0.02 (s, 9H).
Reaction SMILES: C1(C)C(S(O)(=O)=O)=CC=CC=1.COC1C=CC(N2C(=O)[C:25]3=[CH:26][CH:27]=[C:28]4[C:35]5=[CH:36][CH:37]=[C:38]6C(=O)N(C7C=CC(OC)=CC=7)C(=O)[C:40]7[CH:41]=[CH:42][C:33](=[C:34]5[C:39]6=7)[C:30]5[CH:31]=[CH:32][C:23](=[C:24]3[C:29]4=5)C2=O)=CC=1>O>[CH:36]1[C:35]2=[C:34]3[C:33]([C:30]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][C:28]2=5)[CH:23]=[CH:32][CH:31]=4)=[CH:42][CH:41]=[CH:40][C:39]3=[CH:38][CH:37]=1
Reactant: COc1ccc(N2C(=O)c3ccc4c5ccc6c7c(ccc(c8ccc(c3c48)C2=O)c75)C(=O)N(c2ccc(OC)cc2)C6=O)cc1
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: O
Product: c1cc2cccc3c4cccc5cccc(c(c1)c23)c54
Temperature: 140 °C
Reaction time: 0.33 h

Procedure:
Toluene sulfonic acid (TSA, monohydrate, 250 g) was heated in a kettle to 115 to 120° C. until melted and perylene red 179 (83.3 g) was charged to the kettle at a rate of 10 g per 2 minutes. Upon completion of the charge, the mixture was stirred for 20 minutes and held at 115-120° C. for 2 hours. The reaction medium was allowed to solidify on cooling and reheated to 115 to 120° C. for another 6 hours to yield a conditioned pigment. Ice (500 g) and water (1L) were then added to the hot mixture with vigorous stirring. The resulting slurry was filtered and washed until it became a neutral presscake. The presscake was reslurried into three times its weight of water and placed in a pressure reactor. The slurry was heated to 140° C. under increased pressure for 4 hours cooled then treated with mineral spirits (80 g). The mixture was filtered, washed and dried to give a further conditioned perylene pigment product.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:15](=[O:17])[CH:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[O:12][C:11]=2[C:10]([CH2:22][CH2:23][CH3:24])=[C:9]2[C:4]=1[CH2:5][CH2:6][CH2:7][CH2:8]2.CC(C)=[O:27]>O.S(=O)(=O)(O)O.[O-2].[O-2].[O-2].[Cr+6]>[CH3:1][O:2][C:3]1[C:16]2[C:15](=[O:17])[CH:14]=[C:13]([C:18]([O:20][CH3:21])=[O:19])[O:12][C:11]=2[C:10]([CH2:22][CH2:23][CH3:24])=[C:9]2[C:4]=1[CH2:5][CH2:6][CH2:7][C:8]2=[O:27]
Reactant: CC(C)=O
Reactant: CCCc1c2c(c(OC)c3c(=O)cc(C(=O)OC)oc13)CCCC2
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Agent: [O-2]
Solvent: O
Product: CCCc1c2c(c(OC)c3c(=O)cc(C(=O)OC)oc13)CCCC2=O

Procedure:
Methyl 6,7,8,9-tetrahydro-5-methoxy-4-oxo-10-propyl-4H-naphtho-[2,3-b]pyran-2-carboxylate (81.4 g; 0.25 mole) was dissolved in acetone (1 l) and stirred rapidly while adding a solution of chromium trioxide (220 g) in water (830 ml) and concentrated sulphuric acid (190 ml), adding at such a rate that the acetone refluxed gently. The mixture was then stirred at room temperature overnight, poured into water (1 l) and extracted into chloroform (3×). The organic fractions were combined, dried (sodium sulphate) and evaporated to give a yellow oil which was submitted to high pressure liquid chromatography (HPLC) to separate the components.