Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([NH:8][C@@H:9]([CH2:15][CH2:16][C:17]([C:19]1[CH:20]=[N:21][CH:22]=[C:23]([F:25])[CH:24]=1)=O)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=O)(C)(C)C.C(O)(C(F)(F)F)=O>>[F:25][C:23]1[CH:24]=[C:19]([C:17]2[CH2:16][CH2:15][C@@H:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[N:8]=2)[CH:20]=[N:21][CH:22]=1
Reactant: CCOC(=O)[C@H](CCC(=O)c1cncc(F)c1)NC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)[C@@H]1CCC(c2cncc(F)c2)=N1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 83.4 %

Procedure:
(S)-ethyl 2-(tert-butoxycarbonylamino)-5-(5-fluoropyridin-3-yl)-5-oxopentanoate (4.80 g, 13.55 mmol) was treated with TFA (24 mL) and the mixture was stirred at ambient temperature for 45 minutes. The mixture was concentrated and the residue was dissolved in H2O (10 mL) and EtOAc (50 mL) was added. The mixture was treated slowly with saturated aqueous K2CO3 (15 mL). The aqueous layer was separated and the organic layer was washed with 10% aqueous NH4Cl. The EtOAc layer was concentrated to give crude (S)-ethyl 5-(5-fluoropyridin-3-yl)-3,4-dihydro-2H-pyrrole-2-carboxylate as an amber oil (2.67 g, 83% yield). The oil was dissolved in isopropyl alcohol (20 mL) and was treated with 10% Pd/C (0.266 g, 0.250 mmol). The reaction vessel was purged with hydrogen gas (3×) and mixture was stirred at ambient temperature under 1 atm of hydrogen for 16 hours. The reaction was purged with nitrogen and filtered through a Celite pad. The filtrate was concentrated to furnish the title compound as an amber oil that began to solidify upon standing (2.58 g, 96%).
Reaction SMILES: [O-]CC.[Na+].[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6]([O:8]CC)=O.[C:15]([C:19]1[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[CH:21][CH:20]=1)([CH3:18])([CH3:17])[CH3:16]>C(O)C.C1(C)C=CC=CC=1>[C:15]([C:19]1[CH:20]=[CH:21][C:22]([C:25](=[O:27])[CH2:26][C:6](=[O:8])[C:5]([O:12][CH2:13][CH3:14])=[O:11])=[CH:23][CH:24]=1)([CH3:18])([CH3:16])[CH3:17]
Reactant: CC(=O)c1ccc(C(C)(C)C)cc1
Reactant: CCOC(=O)C(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=O)CC(=O)c1ccc(C(C)(C)C)cc1
Yield: 100 %

Procedure:
To a cooled solution, <5° C., of sodium ethoxide (4.4 g, 64.6 mmol) in ethanol, diethyl oxalate (7.71 mL, 56.7 mmol) in toluene (150 mL) was added. The reaction mixture was stirred for 30 min, before the addition of 1-(4-tert-butylphenyl)ethanone (56.7 mmol, 10 g) dropwise in toluene (20 mL) (via pressurised dropping funnel). The reaction mixture was stirred overnight to room temperature and then evaporated to low volume. Acetic acid was added and the resultant precipitate was filtered and washed with heptane to obtain ethyl 4-(4-tert-butylphenyl)-2,4-dioxobutanoate (15.68 g, 56.7 mmol).
Reaction SMILES: [C:1]([NH:6][C:7]1[CH:8]=[C:9]([C:13]2[N:22]=[C:21]([NH:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[N:29]([C:33]([O-:35])=[O:34])[N:28]=[CH:27]4)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([OH:36])[CH:19]=3)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)(=[O:5])[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:44][CH2:45][Cl:46]>CN(C=O)C>[C:1]([NH:6][C:7]1[CH:8]=[C:9]([C:13]2[N:22]=[C:21]([NH:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[N:29]([C:33]([O:35][C:9]([CH3:13])([CH3:10])[CH3:8])=[O:34])[N:28]=[CH:27]4)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:36][CH2:44][CH2:45][Cl:46])[CH:19]=3)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: ClCCBr
Reactant: CCCC(=O)Nc1cccc(-c2nc(Nc3ccc4c(cnn4C(=O)[O-])c3)c3cc(O)ccc3n2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCC(=O)Nc1cccc(-c2nc(Nc3ccc4c(cnn4C(=O)OC(C)(C)C)c3)c3cc(OCCCl)ccc3n2)c1
Temperature: 85 °C
Yield: 111.8 %

Procedure:
To a mixture of 5-(2-(3-butyramidophenyl)-6-hydroxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (1.50 g, 2.79 mmol) and potassium carbonate (1.64 g, 11.8 mmol) in anhydrous DMF (5 mL) was added 1-bromo-2-chloroethane (1.6 g, 11.2 mmol) The subsequent mixture was heated at 85° C. for 4 h, upon which it was allowed to cool to RT and it was poured onto ice-water. A solid was precipitated out, which collected via filtration and dried under vacuum. The solid was purified via silica gel column chromatography to give tert-butyl 5-(2-(3-butyramidophenyl)-6-(2-chloroethoxy)-quinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.94 g, 1.56 mmol, 60%). HPLC retention time 7.479.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([C@@H:16]3[CH2:20][CH2:19][CH2:18][NH:17]3)[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[C:21]([O:25][C:26]([NH:28][C@@H:29]([CH2:33][CH2:34][CH2:35][CH2:36][NH:37][C:38]([O:40][CH2:41][CH:42]1[C:54]2[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=2[C:48]2[C:43]1=[CH:44][CH:45]=[CH:46][CH:47]=2)=[O:39])[C:30](O)=[O:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].C(N(C(C)C)C(C)C)C.N1(O)C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[CH:44]1[C:43]2[CH:42]([CH2:41][O:40][C:38](=[O:39])[NH:37][CH2:36][CH2:35][CH2:34][CH2:33][C@H:29]([NH:28][C:26]([O:25][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:27])[C:30]([N:17]3[CH2:18][CH2:19][CH2:20][C@H:16]3[C:14]3[CH:13]=[N:12][CH:11]=[C:10]([C:8](=[O:9])[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[CH:15]=3)=[O:31])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:48]=2[CH:47]=[CH:46][CH:45]=1
Reactant: O=C(c1ccc(F)cc1)c1cncc([C@@H]2CCCN2)c1
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)N1CCC[C@H]1c1cncc(C(=O)c2ccc(F)cc2)c1
Reaction time: 16 h

Procedure:
To a solution of (4-fluoro-phenyl)-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-methanone (1.0 g, 3.7 mmol), (S)-2-tert-butoxycarbonylamino-6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid (2.0 g, 4.4 mmol) and ethyldiisopropylamine (3 mL) in DMF (20 mL) was added a solution of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (1.67 g, 4.4 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol (0.6 g, 4.4 mmol) in DMF (10 mL) and the mixture was shaken for 16 hours. The reaction mixture was diluted with ethyl acetate (300 mL), washed sequentially with brine (2×) (300 mL), saturated aqueous bicarbonate solution (300 mL), brine (300 mL), water (300 mL), and brine (300 mL), then dried over Na2SO4/MgSO4, and concentrated in vacuo to provide crude ((S)-5-tert-butoxycarbonylamino-6-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 9H-fluoren-9-ylmethyl ester as a light yellow foam.
Reaction SMILES: [CH3:1][Si:2](Br)([CH3:4])[CH3:3].C[O:7][P:8]([C:12](=[O:21])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:11])[O:9]C>>[CH3:1][Si:2]([O:7][P:8]([C:12](=[O:21])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:11])[O:9][Si:2]([CH3:4])([CH3:3])[CH3:1])([CH3:4])[CH3:3]
Reactant: C[Si](C)(C)Br
Reactant: COP(=O)(OC)C(=O)CCc1ccccc1
Product: C[Si](C)(C)OP(=O)(O[Si](C)(C)C)C(=O)CCc1ccccc1
Reaction time: 1 h

Procedure:
10.7 g of trimethylsilyl bromide were added dropwise at room temperature over a period of 1 hour to 8.5 g of dimethyl(3-phenylpropionyl)phosphonate. The mixture was then stirred for a further 1 hour and then evaporated at 30° C./0.1 mm Hg to give 12.5 g of bis(trimethylsilyl)-(3-phenylpropionyl)phosphonate in the form of a pale yellow oil. This oil was used in the next step without further purification.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[N+:27]([O-:29])=[O:28])[N:15]=2)[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.NC1CCCN(C2C=CN=C(NC3C=CC=CC=3[N+]([O-])=O)N=2)C1.[CH2:61]([S:64](Cl)(=[O:66])=[O:65])[CH2:62][CH3:63].C(N(CC)CC)C>C(Cl)Cl>[N+:27]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[NH:20][C:16]1[N:15]=[C:14]([N:10]2[CH2:11][CH2:12][CH2:13][CH:8]([NH:7][S:64]([CH2:61][CH2:62][CH3:63])(=[O:66])=[O:65])[CH2:9]2)[CH:19]=[CH:18][N:17]=1)([O-:29])=[O:28]
Reactant: CC(C)(C)OC(=O)NC1CCCN(c2ccnc(Nc3ccccc3[N+](=O)[O-])n2)C1
Reactant: CCCS(=O)(=O)Cl
Agent: NC1CCCN(c2ccnc(Nc3ccccc3[N+](=O)[O-])n2)C1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCCS(=O)(=O)NC1CCCN(c2ccnc(Nc3ccccc3[N+](=O)[O-])n2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 25.2 %

Procedure:
To a solution tert-butyl(1-(2-((2-nitrophenyl)amino)pyrimidin-4-yl)piperidin-3-yl)carbamate (0.14 g, 0.34 mmol) in DCM (2.0 mL) was added TFA (1.0 mL) and the mixture was stirred for 1 h. An aliquot of the reaction mixture was analyzed by LCMS, which indicated that the reaction had proceeded to completion. The solvents were removed and the residue was dried on high vacuum. The crude product was used for the next step without further purification. To a solution of 4-(3-aminopiperidin-1-yl)-N-(2-nitrophenyl)pyrimidin-2-amine (0.34 mmol) in DCM (3.5 mL) at 0° C. was added propane-1-sulfonyl chloride (0.045 mL, 0.4 mmol) and triethylamine (0.12 mL, 0.85 mmol) and the mixture was warmed to room temperature overnight. The crude reaction mixture was concentrated and purified by flash chromatography (0-7.5% MeOH/DCM) to give the title compound (36 mg, 24% yield). MS (ES+) C18H24N6O4S requires: 420. found: 421 [M+H]+.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][Br:7].[Cl:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[C:11]([Cl:18])[C:10]=1[OH:19]>>[Br:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][O:19][C:10]1[C:11]([Cl:18])=[CH:12][C:13]([N+:15]([O-:17])=[O:16])=[CH:14][C:9]=1[Cl:8]
Reactant: O=[N+]([O-])c1cc(Cl)c(O)c(Cl)c1
Reactant: BrCCCCCBr
Product: O=[N+]([O-])c1cc(Cl)c(OCCCCCBr)c(Cl)c1

Procedure:
In a manner similar to Preparation 40 react 1,5-dibromopentane with 2,6-dichloro-4-nitrophenol to obtain the title compound.
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1.[C:13]1([S:19]([O-:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[C:13]1([S:19]([C:3]2[CH:2]=[C:1]([OH:12])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4]=2[OH:11])(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=S([O-])c1ccccc1
Reactant: O=C1C=CC(=O)c2ccccc21
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: O=S(=O)(c1ccccc1)c1cc(O)c2ccccc2c1O
Reaction time: 5 h

Procedure:
1,4-naphthoquinone (15.8 g) was dissolved in 100 ml of a mixture of ethyl acetate and acetic acid (9:1) and sodium benzenesulfinate (24.6 g) was added. The resulting mixture was stirred for 5 hours and the obtained crystals were filtered and washed with a small amount of acetone. (Yield: 22.5 g)
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[N:19]1([C:24]2[CH:33]=[CH:32][C:27]([C:28]([NH:30][NH2:31])=[O:29])=[CH:26][CH:25]=2)[CH:23]=[CH:22][CH:21]=[N:20]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([NH:31][NH:30][C:28](=[O:29])[C:27]2[CH:26]=[CH:25][C:24]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:33][CH:32]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: NNC(=O)c1ccc(-n2cccn2)cc1
Reactant: Cc1c(N[C@@H](C(=O)O)[C@H](C)O)ccc(C#N)c1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(N[C@@H](C(=O)NNC(=O)c2ccc(-n3cccn3)cc2)[C@H](C)O)ccc(C#N)c1Cl
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a pre-cooled (−45° C.) solution of (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (134 mg, 0.50 mmol) and 4-(1H-pyrazol-1-yl)benzohydrazide (101 mg, 0.50 mmol) in anhydrous THF (10 mL) was added 1-Hydroxybenzotriazole monohydrate (77 mg, 0.50 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide-HCl (192 mg, 1.00 mmol) at −45° C. followed by triethylamine (0.14 mL, 1.00 mmol). The reaction mixture warmed to room temperature and stirred for 48 h, then quenched with 5% aq. citric acid (30 mL). The solution was extracted with EtOAc (30 mL). The organic extract was washed with 5% aq. Citric acid (2×20 mL), sat. aq. NaHCO3 (3×20 mL), H2O (2×20 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as an off white solid (164 mg, 73%): 1H NMR (400 MHz, CDCl3, δ in ppm) 8.85 (br s, 1H), 7.99 (d, J=2.5 Hz, 1H), 7.89 (d, J=8.6 Hz, 2H), 7.80-7.72 (m, 3H), 7.37 (dd, J=3.7, 8.2 Hz, 1H), 6.54-6.50 (m, 1H), 6.45 (dd, J=5.7, 8.6 Hz, 1H), 5.25 (d, J=6.3 Hz, 1H), 4.71 (br s, 1H), 4.53-4.45 (m, 1H), 2.32 (s, 3H), 1.36 (d, J=6.3 Hz, 3H).
Reaction SMILES: [CH2:1]=[CH:2][CH3:3].C=C.[CH:6]([C:9]1C=CC=[CH:11][C:10]=1[O:15][CH3:16])=[CH:7]C>C1(OC)C=CC=CC=1>[CH:2]([C:3]1[CH:11]=[C:10]([O:15][CH3:16])[CH:9]=[CH:6][CH:7]=1)=[CH2:1]
Reactant: CC=Cc1ccccc1OC
Reactant: C=CC
Agent: C=C
Solvent: COc1ccccc1
Product: C=Cc1cccc(OC)c1
Temperature: 180 °C
Reaction time: 16 h

Procedure:
In this experiment propylene is charged into a reactor containing an ethylenation reaction mixture that has been allowed to run long enough to demonstrate catalytic activity similar to what is observed in the ethylenation reaction catalyzed by (CH3)5CpRh(CO)2This procedure is followed because it is feared that propylene might be so much less reactive than ethylene that even small inhibiting influences might interfere with the detection of propenylanisole. Thus, an ethylenation reaction is set up as follows: the sealed autoclave containing a glass liner that has been oven dried is purged with argon. A 10-ml anisole solution of 147 mg (0.5 mmole) of the Rh catalyst is introduced by syringe through a dip tube capped with a rubber septum. Another 50 ml of anisole is added the same way. After purging with argon again, the reactor is pressurized with ethylene to 500 psig at room temperature. The temperature is raised to 180° C. (at 680 psig) and, over a four-hour period, both GLC-mass spectral analysis and the change of color from red to yellow reveal the conversion of the initially charged dicarbonyl rhodium complex to (CH3)5CpRh(C2H4)2. After an additional 16 hours at 175° C., a small amount of m-vinylanisole is detected. An additional 2 hours at 190° C. results in considerably more rapid production of m-vinylanisole. At this point the reactor is cooled then vented then charged with propylene. After 1.5 turnovers, the selectivity to m-vinylanisole is 85 percent. Samples from this point on are deep blue in color. The temperature is raised to 200° C. (at 330 psig) over a two-hour period and held there for an additional 2 hours. GLC-mass spectral analysis indicates the production of small amounts of propenylanisole. The temperature is raised again to 210° C. and held there 21 hours then to 220° C. for an additional 16 hours. During this time GLC and GLC-mass spectral analysis indicate the production of about 100 mg of a mixture of two isomers of propenylanisole.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH2:27])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH2:28]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37](Br)[CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:37]4[CH:38]=[CH:39][CH:40]=[C:35]([CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH:36]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: Brc1cccc(Cc2ccccc2)c1
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N)cc3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(Cc5ccccc5)c4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 41, Step 2, using 1-[4′-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 1-benzyl-3-bromo-benzene.
Reaction SMILES: [OH:1][C:2]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[C:12]2[C:11]3[CH:10]=[CH:9][C:8]([CH3:20])=[CH:7][C:6]=3[CH:5]([C:21]([OH:23])=[O:22])[C:4]=2[CH:3]=1.[CH3:24]O>OS(O)(=O)=O>[OH:1][C:2]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[C:12]2[C:11]3[CH:10]=[CH:9][C:8]([CH3:20])=[CH:7][C:6]=3[CH:5]([C:21]([O:23][CH3:24])=[O:22])[C:4]=2[CH:3]=1
Reactant: Cc1ccc2c(c1)C(C(=O)O)c1cc(O)c3cc(C)ccc3c1-2
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)C1c2cc(C)ccc2-c2c1cc(O)c1cc(C)ccc21
Temperature: 25 °C

Procedure:
The product of Step 2 (4.5 g) was dissolved in MeOH (200 mL) and 3 drops of H2SO4 were added. The mixture was heated to reflux for 3 hrs and cooled to room temperature. After evaporation of the solvent, the resulting residue was dissolved in DCM (150 mL) and washed with brine (50 mL). The organic layer was collected and the solvent evaporated to afford the product methyl 5-hydroxy-3,9-dimethyl-7H-benzo[c]fluorene-7-carboxylate (4.5 g). MS analysis supported the molecular weight of the product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:18]([CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:17]3[C:12]([C:13]4[CH:27]=[CH:26][C:25]([C:28]([OH:30])=[O:29])=[CH:24][C:14]=4[CH2:15][CH2:16]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[C:31]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)(=[O:34])[CH2:32]O>>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH:18]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23]3)[CH:17]3[C:12]([C:13]4[CH:27]=[CH:26][C:25]([C:28]([O:30][CH2:32][C:31]([O:35][CH2:36][C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)=[O:34])=[O:29])=[CH:24][C:14]=4[CH2:15][CH2:16]3)=[N:11]2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]
Reactant: N#Cc1ccc(N2N=C3c4ccc(C(=O)O)cc4CCC3C2C2CCCC2)cc1Cl
Reactant: O=C(CO)OCc1ccccc1
Product: N#Cc1ccc(N2N=C3c4ccc(C(=O)OCC(=O)OCc5ccccc5)cc4CCC3C2C2CCCC2)cc1Cl

Procedure:
The title compound was prepared from (±)-(3SR,3aRS)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid, Example 15 and benzyl glycolate according to Method E. 1H NMR (400 MHz, CDCl3) δ ppm 1.20-1.68 (m, 7H), 1.72-1.84 (m, 1H), 1.96 (ddd, J=26.18, 12.89, 4.16 Hz, 1H), 2.06-2.20 (m, 1H), 2.25-2.35 (m, 1H), 2.84-2.98 (m, 1H), 3.12 (ddd, J=15.91, 3.36, 3.02 Hz, 1H), 3.49 (ddd, J=113.83, 9.40, 4.70 Hz, 1H), 4.65 (dd, J=9.40, 5.37 Hz, 1H), 4.92 (s, 2H), 5.25 (s, 2H), 7.03 (dd, J=8.73, 2.01 Hz, 1H), 7.31 (d, J=2.15 Hz, 1H), 7.33-7.42 (m, 5H), 7.46 (d, J=8.86 Hz, 1H), 7.93-8.03 (m, 2H), 8.17 (d, J=8.59 Hz, 1H).
Reaction SMILES: [Mg].[Si](O[Si](C(C)(C)C)(C)C)(C(C)(C)C)(C)C.Br[C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.[CH2:25]([C:27]1[N:28]=[C:29]2[C:34]([CH3:35])=[CH:33][C:32]([CH3:36])=[N:31][N:30]2[C:37]=1[CH:38]=[O:39])[CH3:26]>C1COCC1.CCOC(C)=O.CCCCCC>[CH2:25]([C:27]1[N:28]=[C:29]2[C:34]([CH3:35])=[CH:33][C:32]([CH3:36])=[N:31][N:30]2[C:37]=1[CH:38]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[OH:39])[CH3:26]
Reactant: CCc1nc2c(C)cc(C)nn2c1C=O
Reactant: Oc1ccc(Br)cc1
Agent: CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C
Agent: [Mg]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCc1nc2c(C)cc(C)nn2c1C(O)c1ccc(O)cc1
Temperature: 35 °C
Yield: 82 %

Procedure:
A 100 mL three necked round bottom flask equipped with a magnetic stir bar, septum, reflux condenser and a nitrogen inlet was dried and charged with 0.608 g (25 mmol) of magnesium turnings and 15 mL of dry THF. A solution of 7.182 g (25 mmol) of the t-butyldimethylsilylether derived from 4-bromophenol dissolved in 10 mL of dry THF was added via syringe and the reaction mixture was stirred at reflux for 3 hours. A separate 50 mL flask equipped with a magnetic stir bar, septum and containing a solution of 0.747 g (3.7 mmol) of the product of Step C was stirred at 0° C. in an ice-water bath. The Grignard reaction mixture was cooled to 35° C. and 5 mL (5 mmol) of the approximately 1.0M solution was transferred to the second reaction mixture via syringe. The reaction mixture was stirred at 0° C. for 30 min, at which point TLC analysis (50% EtOAc-hexane) indicated complete reaction of the aldehyde. The reaction mixture was quenched with 10% aqueous sodium bisulfate, then partitioned between THF and saturated brine. The organic layer was separated, evaporated in vacuo, redissolved in THF, dried (MgSO4), filtered and concentrated to an oil. The residual oil was again redissolved in 10 mL THF and treated with 5 mL of a 1.0M solution of tetra-n-butylammonium fluoride in THF. After stirring 1 h at room temperature the reaction mixture was evaporated in vacuo, and the residual oil was purified by filtration through a short plug of silica gel eluted with THF. The filtrate was concentrated and the product was precipitated from THF/hexane to afford 0.896 g (82%) of title compound as an off-white crystalline solid.
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>O>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 133 °C

Procedure:
2,5-dianilino-terephthalic acid (one part) was dissolved in polyphosphoric acid (6.14 parts at 118.5%). The solution, already at 105° C., was heated to 133° C. for 3 hours then cooled to 100° C. and diluted to a fluid mass with water (0.5 parts). The solution was then drowned into methanol (11.6 parts) and the mixture heated at 125° C. for one hour to obtain a bluish red beta-phase quinacridone pigment.
Reaction SMILES: [CH2:1]([C:3]1[C:7]2[CH:8]=[N:9][C:10]([C:12]([O:14]CC)=O)=[CH:11][C:6]=2[N:5]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH:4]=1)[CH3:2].[OH-].[Na+].Cl.[CH3:25][NH:26][O:27][CH3:28]>>[CH2:1]([C:3]1[C:7]2[CH:8]=[N:9][C:10]([C:12]([N:26]([O:27][CH3:28])[CH3:25])=[O:14])=[CH:11][C:6]=2[N:5]([CH2:17][CH2:18][CH2:19][O:20][CH3:21])[CH:4]=1)[CH3:2]
Reactant: CCOC(=O)c1cc2c(cn1)c(CC)cn2CCCOC
Reactant: CNOC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CCc1cn(CCCOC)c2cc(C(=O)N(C)OC)ncc12

Procedure:
Ethyl 3-ethyl-1-(3-methoxypropyl)-1H-pyrrolo[3,2-c]pyridine-6-carboxylate was treated with aqueous sodium hydroxide solution and N,O-dimethylhydroxyamine hydrochloride in the similar manner to Reference Example 105(7) to give 3-ethyl-N-methoxy-1-(3-methoxypropyl)-N-methyl-1H-pyrrolo[3,2-c]pyridine-6-carboxamide [REx(106-3)] as a pale yellow oil.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]=O.[CH:13]([CH:15]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:14].CCCCCCC.CCOC(C)=O>C(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1/[CH:11]=[CH:15]/[CH:13]=[O:14]
Reactant: O=CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccc2ccccc2n1
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Solvent: ClCCl
Product: O=C/C=C/c1ccc2ccccc2n1
Yield: 11.3 %

Procedure:
A solution of quinolin-2-carboxaldehyde (3.5 g, 22.3 mmol) and formylmethylenetriphenylphosphorane (6.79 g, 22.3 mmol) in CH2Cl2 (180 ml) was treated as seen in preparation 1. After a chromatography on silicagel (n-heptane/EtOAc 4/1) pure title compound was obtained (460 mg, 2.51 mmol, yield 11.3%) as grey needles, m.p.=85°.