Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:4]([CH:10]([CH3:19])[C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=O)[CH3:2].C([O-])(=O)C.[NH4+:24]>>[CH3:2][C:1]1[NH:24][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:10]([CH3:19])[C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: [NH4+]
Reactant: CCOC(=O)C(C(C)=O)C(C)C(=O)c1ccccc1
Agent: CC(=O)[O-]
Product: CCOC(=O)c1c(C)[nH]c(-c2ccccc2)c1C
Yield: 90.8 %

Procedure:
Using ethyl 2-acetyl-3-methyl-4-oxo-4-phenylbutanoate (20.3 g) and ammonium acetate (6.61 g), a procedure as in Reference Example 14 was performed to give the title compound as a brown oil (yield 17.1 g, 91%).
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].C(N(CC)CC)C.C(Cl)Cl.[OH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([S:24][CH3:25])[C:19]=1[N+:26]([O-:28])=[O:27]>O>[S:1]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([S:24][CH3:25])[C:19]=1[N+:26]([O-:28])=[O:27])([CH3:4])(=[O:3])=[O:2]
Reactant: CSc1cccc(CO)c1[N+](=O)[O-]
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CSc1cccc(COS(C)(=O)=O)c1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
76 mg (0.66 mmol) of mesyl chloride and then 69 mg (0.68 mmol) of triethylamine were added to 5 ml of a methylene chloride solution containing 100 mg (0.50 mmol) of 2-hydroxymethyl-6-methylthio-1-nitro-benzene, in an ice bath. The mixture was stirred at the temperature of the ice bath for 1 hour and 15 minutes. At the end of this time, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic extract was separated and washed with 2N aqueous hydrochloric acid and then with water. The solvent was then removed by distillation under reduced pressure, to obtain the title compound. This product was used for the next step without purification.
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:13]=1[C:14]([OH:16])=O)/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])\[CH3:4].[NH2:23][CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][N:26]1[CH2:30][CH3:31]>>[CH2:30]([N:26]1[CH2:27][CH2:28][CH2:29][CH:25]1[CH2:24][NH:23][C:14](=[O:16])[C:13]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:12]=1[O:11][CH2:1]/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])\[CH3:4])[CH3:31]
Reactant: CCN1CCCC1CN
Reactant: COc1ccc(OC/C=C(\C)CCC=C(C)C)c(C(=O)O)c1
Product: CCN1CCCC1CNC(=O)c1cc(OC)ccc1OC/C=C(\C)CCC=C(C)C
Yield: 86 %

Procedure:
In a manner identical to Example 15, 2-geranyloxy-5-methoxybenzoic acid(1.52 g) was subjected to a condensation reaction with 2-aminomethyl-1-ethylpyrrolidine (0.7 ml), thereby yielding 1.78 g(86%) of the aimed compound.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH2:5]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[CH:26][CH:27]=3)=[CH:19][CH:20]=2)[C:15]([CH2:29][NH2:30])=[CH:14]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(N(CC)CC)C>C1COCC1>[CH2:5]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[CH:26][CH:27]=3)=[CH:19][CH:20]=2)[C:15]([CH2:29][NH:30][C:1](=[O:3])[CH3:2])=[CH:14]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CC(=O)Cl
Reactant: CCCCCCCCn1cc(CN)c2cc(-c3cccc(C)c3)ccc21
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCCCn1cc(CNC(C)=O)c2cc(-c3cccc(C)c3)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
Acetyl chloride (44 μl, 0.434 mmol) was added to a solution of (1-octyl-5-m-tolyl-1H-indol-3-yl)methanamine (220 mg, 0.628 mmol) and triethylamine (131 μl, 0.651 mmol) in THF (4 mL) at 0° C. The reaction mixture was allowed to stir at room temp for 60 min, the precipitate formed was filtered off, the filtrate was concentrated, and the residue was subjected to column chromatography (silica gel, CH2Cl2) to give sulphonamide 23 in 65% yield.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([Mg]Br)=[CH:12][CH:11]=1.Cl>O1CCCC1>[F:9][C:10]1[CH:15]=[CH:14][C:13]([CH:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[OH:8])=[CH:12][CH:11]=1
Reactant: Fc1ccc([Mg]Br)cc1
Reactant: O=Cc1ccccc1
Agent: Cl
Solvent: C1CCOC1
Product: OC(c1ccccc1)c1ccc(F)cc1
Temperature: 25 °C
Yield: 80.4 %

Procedure:
Benzaldehyde (8.5 g, 80 mmol) was dissolved in 100 mL of tetrahydrofuran and cooled in an ice bath. Then, a 1.0-M solution (88 mL, 88 mmol) of 4-fluorophenylmagnesium bromide in tetrahydrofuran was added dropwise thereto at 0° C. After the dropping was completed, the mixture was heated to a room temperature, and the completion of the reaction was confirmed by TLC. After the completion of the reaction, the reaction mixture was poured into 5% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate, and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (chloroform/ethanol (volume ratio)=10:1) to give the title compound (13 g, 81%).
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:12]2[C@@H:11]3[C@@H:6]([N:7]([C:15]([C:17]4[CH:25]=[CH:24][C:20]5[NH:21][CH:22]=[N:23][C:19]=5[CH:18]=4)=[O:16])[CH2:8][CH2:9][CH2:10]3)[CH2:5][C:4]=2[C:3]=1[OH:26].C(OCC)(OCC)O[CH2:29][CH3:30]>>[NH:21]1[C:20]2[CH:24]=[CH:25][C:17]([C:15]([N:7]3[C@H:6]4[C@H:11]([C:12]5[CH:4]=[C:3]6[O:26][C:29]([CH3:30])=[N:1][C:2]6=[CH:14][C:13]=5[CH2:5]4)[CH2:10][CH2:9][CH2:8]3)=[O:16])=[CH:18][C:19]=2[N:23]=[CH:22]1
Reactant: CCOC(OCC)OCC
Reactant: Nc1ccc2c(c1O)C[C@H]1[C@@H]2CCCN1C(=O)c1ccc2[nH]cnc2c1
Product: Cc1nc2cc3c(cc2o1)[C@@H]1CCCN(C(=O)c2ccc4[nH]cnc4c2)[C@@H]1C3
Temperature: 25 °C
Yield: 64 %

Procedure:
(cis-7-Amino-8-hydroxy-2,3,4,4a,9,9a-hexahydro-indeno[2,1-b]pyridin-1-yl)-(1H-benzoimidazol-5-yl)-methanone (0.10 g) in triethyl orthoformate (0.5 mL) is stirred at 60° C. for 2 h. After cooling to room temperature, the mixture is concentrated and the residue is chromatographed on silica gel (dichloromethane/methanol 1:0→7:3) to afford the title compound. Yield: 64% of theory; LC (method 1): tR=2.28 min; Mass spectrum (ESI+): m/z=373 [M+H]+.
Reaction SMILES: [CH3:1][CH:2]1[CH2:18][CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)[N:9]=[C:4]2[NH:3]1.[H-].[Na+].[N:21]1[C:29]2[CH2:28][C@H:27]([CH2:30]OS(C)(=O)=O)[CH2:26][C:25]=2[CH:24]=[CH:23][CH:22]=1.O>CN(C)C=O>[N:21]1[C:29]2[CH2:28][C@H:27]([CH2:30][N:3]3[C:4]4=[N:9][C:8]([C:10]5[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=5)=[CH:7][C:6](=[O:16])[N:5]4[CH2:17][CH2:18][CH:2]3[CH3:1])[CH2:26][C:25]=2[CH:24]=[CH:23][CH:22]=1
Reactant: CC1CCn2c(nc(-c3ccncc3)cc2=O)N1
Reactant: CS(=O)(=O)OC[C@@H]1Cc2cccnc2C1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1CCn2c(nc(-c3ccncc3)cc2=O)N1C[C@@H]1Cc2cccnc2C1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 60.5 %

Procedure:
To a solution of 0.15 g (0.62 mmol) of 8-methyl-2-(pyridin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one in 3 ml of anhydrous dimethylformamide was added 0.032 g (0.81 mmol) of sodium hydride (60% suspension in mineral oil). The mixture was allowed to stir at 50° C. for 30 min. 0.184 g (0.81 mmol) of methanesulfonic acid 6,7-dihydro-5H-[1]pyrindin-6-(R)-ylmethyl ester was added and the stirring continued at 85° C. for 18 h. Water was added and the mixture extracted with trichloromethane/methanol 90/10. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel, eluting with a mixture of ethylacetate/ethanol in the proportions 100/0 to 74/26, gives 0.14 g (60%) of the compound in the form of free base.
Reaction SMILES: [CH2:1]([NH:4][C:5]1[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][N:8]=[C:7]2[CH:16]=[N:17][NH:18][C:6]=12)[CH:2]=[CH2:3].[CH3:19][O:20][C:21](OC)([CH3:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([NH:4][C:5]1[C:6]2[C:7](=[CH:16][N:17]([C:21]([O:20][CH3:19])([CH3:23])[CH3:22])[N:18]=2)[N:8]=[CH:9][C:10]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:2]=[CH2:3]
Reactant: COC(C)(C)OC
Reactant: C=CCNc1c(C(=O)OCC)cnc2cn[nH]c12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCNc1c(C(=O)OCC)cnc2cn(C(C)(C)OC)nc12
Yield: 64.3 %

Procedure:
A mixture of ethyl 7-allylamino-1H-pyrazolo[4,3-b]-pyridine-6-carboxylate (3.69 g, 15 mmol), 2,2-dimethoxypropane (9.2 ml, 75 mmol) and 4-toluenesulphonic acid (142 mg, 0.75 mmol) in acetone (200 ml) was heated under reflux for 48 h. The solution was cooled and stirred with solid potassium carbonate, then filtered and evaporated in vacuo. Column chromatography of the residue on basic alumina (100 g), eluting with ethyl acetate, gave the title compound as a white solid (3.07 g, 64%), m.p. 102°-103° C. Found: C, 60.31; H, 6.78; N, 17.60; C16H22N4O3 requires C, 60.36; H, 6.97; N, 17.60%
Reaction SMILES: N1([C:6](N2C=CN=C2)=[O:7])C=CN=C1.[CH2:13]([OH:18])[CH2:14][CH2:15][CH2:16][CH3:17].[CH3:19][S:20]([C:23]1[CH:28]=[CH:27][C:26]([N:29]2[C:33]3=[N:34][CH:35]=[N:36][C:37]([O:38][CH:39]4[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]4)=[C:32]3[CH:31]=[N:30]2)=[CH:25][CH:24]=1)(=[O:22])=[O:21].C(N(CC)CC)C>CS(C)=O>[CH2:13]([O:18][C:6]([N:42]1[CH2:43][CH2:44][CH:39]([O:38][C:37]2[N:36]=[CH:35][N:34]=[C:33]3[N:29]([C:26]4[CH:27]=[CH:28][C:23]([S:20]([CH3:19])(=[O:21])=[O:22])=[CH:24][CH:25]=4)[N:30]=[CH:31][C:32]=23)[CH2:40][CH2:41]1)=[O:7])[CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CS(=O)(=O)c1ccc(-n2ncc3c(OC4CCNCC4)ncnc32)cc1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCCCCO
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CCCCCOC(=O)N1CCC(Oc2ncnc3c2cnn3-c2ccc(S(C)(=O)=O)cc2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 39.8 %

Procedure:
Di-imidazol-1-yl-methanone (0.51 mmol, 83 mg), and n-pentanol (0.51 mmol, 56 μL) were dissolved in DMSO (1 mL) and stirred for 30 minutes at room temperature. Then, 1-(4-methanesulfonyl-phenyl)-4-(piperidin-4-yloxy)-1H-pyrazolo[3,4-d]pyrimidine (0.17 mmol, 70 mg) and triethylamine (0.51 mmol, 72 μL) were added and heated in a microwave at 120° C. for 6 minutes. The progress of the reaction was monitored by LCMS. The reaction mixture was quenched with water and the product was extracted with ethylacetate. Removal of organic solvents in vacuo and purification by HPLC provided Compound A117 as a white solid (33 mg, 32%). Exact mass calculated for C23H29N5O5S 487.57, found 488.20 (MH+).
Reaction SMILES: [CH:1]([NH:4][CH:5]([CH3:7])C)([CH3:3])C.[Li]CCCC.[CH3:13][C:14]1[CH2:19][CH2:18][CH2:17][CH2:16][N:15]=1.CSC1CCCN=1>C1COCC1>[N:4]1[CH2:1][CH2:3][CH2:7][C:5]=1[CH:13]=[C:14]1[CH2:19][CH2:18][CH2:17][CH2:16][NH:15]1
Reactant: CC(C)NC(C)C
Reactant: CC1=NCCCC1
Agent: CSC1=NCCC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C(=C1CCCCN1)C1=NCCC1
Reaction time: 0.5 h

Procedure:
To a solution of diisopropylamine (6.32 g, 62.52 mmol) in THF (100 mL) was dropwise added n-BuLi (2.89 M, 21.63 mL, 62.52 mmol) at −78° C. under nitrogen. Once all the n-BuLi was added, the temperature was adjusted to −5° C., and the reaction mixture was stirred for 30 min. Then a solution of 2-methyl-3,4,5,6-tetrahydropyridine (3.76 g, 38.70 mmol) in THF (15 mL) was added dropwise to the reaction mixture at −5° C., and then stirred. After 30 min, 2-methylthio-1-pyrroline (3.43 g, 29.77 mmol) was added dropwise over 30 min at −78° C. The reaction mixture was stirred as the temperature was allowed to gradually rise to room temperature, and was continuously stirred at room temperature overnight. THF solvent was removed under reduced pressure, then 30 mL of methanol was added dropwise to the residue. After removing all of the volatile solvent, pentane (2×50 mL) was added to the residue, and the mixture was filtered. Concentration of the filtrate under reduced pressure, followed by vacuum distillation (75° C. at 185 mTorr) delivered 4.1 g of product (84%). 1H NMR (CD2Cl2, 500 MHz): δ 9.64 (s, br, 1H), 4.48 (s, 1H), 3.78 (t, 2H, J=7.3 Hz), 3.27 (t, 2H, J=6.1 Hz), 2.45 (m, 2H), 2.33 (t, 2H, J=6.2 Hz), 1.73 (m, 4H), 1.67 (m, 2H). 13CNMR (CD2Cl2, 125 MHz): δ 173.6, 155.8, 86.5, 60.0, 41.7, 37.9, 29.5, 23.8, 22.7, 21.3.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[NH2:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[C:14]#N.C([O:22]CC)C>BrC(Br)C>[NH2:11][C:12]1[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=1[C:14]([C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1)=[O:22]
Reactant: CCOCC
Reactant: COc1ccc(Br)cc1
Reactant: N#Cc1ccccc1N
Agent: CC(Br)Br
Agent: [Mg]
Product: COc1ccc(C(=O)c2ccccc2N)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 81 %

Procedure:
To a 250 mL round-bottomed flask charged with magnesium (1.646 g, 67.7 mmol) and ethyl ether (47.0 ml) was added two drops of dibromoethane and the mixture was heated to reflux for 15 minutes. p-Bromoanisole (6.35 ml, 50.8 mmol) in diethyl ether (47.0 ml) was slowly added through an addition funnel while a refluxing temperature was maintained. The resulting mixture was heated for 3 hrs, and then cooled to room temperature. A solution of 2-aminobenzonitrile (2 g, 16.93 mmol) in diethyl ether (47.0 ml) was added dropwise over 15 min. After the addition, the mixture was refluxed for 16 hrs. The volume was then reduced by half under reduced pressure and the resulting mixture was quenched slowly with ice (100 g). Next, 6N HCl (10 mL) was then added and the mixture was stirred at room temperature for 16 hrs. The pH was adjusted to pH 8 with 5N NaOH and diluted with saturated NaHCO3 (50 ml). The phases were separated and the aqueous layer was back extracted with ethyl acetate (2×200 mL). The combined organic layers were dried (MgSO4), filtered and concentrated. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 70% solvent A/B=heptane/EtOAc, REDISEP® SiO2 120 g). Concentration of the appropriate fractions provided Intermediate 6A (3.13 g, 81%). 1H NMR (400 MHz, DMSO-d6) δ 7.62-7.55 (m, 2H), 7.34-7.22 (m, 2H), 7.09-7.01 (m, 2H), 6.87-6.78 (m, 3H), 6.53 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 3.85 (s, 3H).
Reaction SMILES: Cl[CH:2]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)P(=O)(OCC)OCC.[F:18][C:19]1[C:20]([CH:33]=O)=[CH:21][C:22]2[C:23]([CH3:32])([CH3:31])[CH2:24][CH2:25][C:26]([CH3:30])([CH3:29])[C:27]=2[CH:28]=1>>[F:18][C:19]1[C:20]([C:33]#[C:2][C:11]2[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=2)=[CH:21][C:22]2[C:23]([CH3:32])([CH3:31])[CH2:24][CH2:25][C:26]([CH3:29])([CH3:30])[C:27]=2[CH:28]=1
Reactant: CCOP(=O)(OCC)C(Cl)c1ccc(C)cc1
Reactant: CC1(C)CCC(C)(C)c2cc(C=O)c(F)cc21
Product: Cc1ccc(C#Cc2cc3c(cc2F)C(C)(C)CCC3(C)C)cc1

Procedure:
Using a process similar to that described in Example 13, 27.7 g (0.1 mole) of diethyl 1-chloro-(4-tolyl)-methylphosphonate, 23.4 g (0.1 mole) of 3-fluoro-2-formyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene and 22.5 g (0.2 mole) of potassium tert.-butylate were reacted for 1 hour to give the title compound. Recrystallization from isopropanol gave 16.4 g (51%) of product of melting point 60°-61° C.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([CH3:27])[C:3]=1[O:4][C:5]1[N:9]([CH3:10])[C:8]2[C:11]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:12][CH:13]=[C:14]([CH:15]=O)[C:7]=2[N:6]=1.[CH3:28][NH2:29].[C:30](O)(=O)[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(=O)(O)[O-].[Na+].C(OCC)(=O)C>[Cl:1][C:2]1[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([CH3:27])[C:3]=1[O:4][C:5]1[N:9]([CH3:10])[C:8]2[C:11]([CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[CH:12][CH:13]=[C:14]([CH2:15][N:29]([CH3:28])[CH2:30][CH3:31])[C:7]=2[N:6]=1
Reactant: CC(=O)O
Reactant: CCC(CC)c1ccc(C=O)c2nc(Oc3c(C)cc(Cl)cc3Cl)n(C)c12
Reactant: CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CCC(CC)c1ccc(CN(C)CC)c2nc(Oc3c(C)cc(Cl)cc3Cl)n(C)c12
Temperature: 25 °C
Reaction time: 48 h
Yield: 70 %

Procedure:
To a mixture of 2-(2,4-dichloro-6-methylphenoxy)-7-(1-ethylpropyl)-1-methyl-1H-benzimidazole-4-carbaldehyde (120 mg, 0.296 mmol), methyl amine (2M tetrahydrofuran solution, 1.48 ml, 2.96 mmol), acetic acid (0.5 ml) and ethyl acetate (2.0 ml) was added sodium triacetoxyborohydride (314 mg, 1.48 mmol) and the reaction mixture was stirred at room temperature for 48 h. The residue was diluted with aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The extracts were washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on alumina with a 5% ethyl acetate/n-hexane to give 93 mg (0.21 mmol, 70%) of the title compound as a white powder.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([CH:10]([OH:12])[CH3:11])[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1[NH:17]C(=O)C.O.[C:23]1(C)[CH:28]=CC(S(O)(=O)=O)=C[CH:24]=1>CC(O)C>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([CH:10]([O:12][CH:23]([CH3:28])[CH3:24])[CH3:11])[C:7]([C:13]([F:14])([F:15])[F:16])=[CH:6][C:5]=1[NH2:17]
Reactant: COC(=O)c1cc(C(C)O)c(C(F)(F)F)cc1NC(C)=O
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)O
Solvent: O
Product: COC(=O)c1cc(C(C)OC(C)C)c(C(F)(F)F)cc1N
Temperature: 80 °C
Reaction time: 18 h
Yield: 43.7 %

Procedure:
A solution of 2-acetylamino-5-(1-hydroxy-ethyl)-4-trifluoromethyl-benzoic acid methyl ester (500 mg, 1.64 mmol) in i-PrOH (5 mL) was treated by addition of p-toluenesulfonic acid monohydrate (99.9 mg, 0.517 mmol) and stirred at 80° C. for 18 h. The reaction mixture was cooled then concentrated in vacuo. The residue was purified by column chromatography (silica gel, 5:1 hexanes/EtOAc) to give title product (69 mg, 14% yield) as colorless crystals. m.p.: 87-90° C., API-ES: m/z 306 [M+H]+.
Reaction SMILES: [S:1]1[C:5]([CH2:6][O:7][C:8]([NH:10][C@H:11]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:12][NH:13][CH2:14][C@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]2[S:32][CH:31]=[N:30][CH:29]=2)=[O:25])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:9])=[CH:4][N:3]=[CH:2]1.[CH3:40][CH:41]([CH3:44])[CH:42]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:40][CH:41]([CH3:44])[CH2:42][N:13]([CH2:14][C@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]1[S:32][CH:31]=[N:30][CH:29]=1)=[O:25])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:12][C@H:11]([NH:10][C:8]([O:7][CH2:6][C:5]1[S:1][CH:2]=[N:3][CH:4]=1)=[O:9])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CC(C)C=O
Reactant: O=C(N[C@@H](CNC[C@@H](Cc1ccccc1)NC(=O)OCc1cncs1)Cc1ccccc1)OCc1cncs1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)CN(C[C@@H](Cc1ccccc1)NC(=O)OCc1cncs1)C[C@@H](Cc1ccccc1)NC(=O)OCc1cncs1
Yield: 45.6 %

Procedure:
The product from Example 31D (80 mg, 0.141 mmol), 2-methylpropanal (15 μl, 0.170 mmol), acetic acid (10 μl, 0.166 mmol), and sodium triacetoxyborohydride (48 mg, 0.226 mmol) were processed as described in Example 27 to provide the title compound (40 mg, 44%). 1H NMR (CDCl3) δ 8.73 (s, 2H), 7.76 (s, 2H), 7.32-7.12 (m, 10H), 5.35 (br s, 2H), 5.18 (q, 4H), 3.97 (br s, 2H), 2.83 (br s, 2H), 2.70 (dd, 2H), 2.41 (t, 2H), 2.21 (dd, 2H), 2.00 (m, 1H), 1.87 (dd, 1H), 0.72 (s, 6H); MS (ESI+) m/z 622 (M+H)+.
Reaction SMILES: [O:1]([C:9]1[CH2:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].[Li][CH2:19][CH2:20][CH2:21][CH3:22].[CH3:23][Si:24]([CH3:27])(Cl)Cl>CCOCC.CCCCCC>[CH3:23][Si:24]([CH3:27])([CH:19]1[C:16]2[C:22](=[CH:11][CH:10]=[CH:9][CH:17]=2)[CH:21]=[C:20]1[O:1][Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3])[CH:17]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[O:1][Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3]
Reactant: C[Si](C)(Cl)Cl
Reactant: [Li]CCCC
Reactant: CC(C)(C)[Si](C)(C)OC1=Cc2ccccc2C1
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(C)(C)[Si](C)(C)OC1=Cc2ccccc2C1[Si](C)(C)C1C(O[Si](C)(C)C(C)(C)C)=Cc2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 42.1 %

Procedure:
To a solution of 2-(tert-butyldimethylsiloxy)indene (12.32 g, 50.0 mmol) in Et2O (50 mL) at 0° C. was added dropwise n-BuLi (20.0 mL of a 2.5 M solution in hexane, 50.0 mmol) and the reaction mixture was stirred overnight at room temperature. The resulting solution was then added dropwise to a solution of dimethyldichlorosilane (3.03 mL, 25.0 mmol) in Et2O (25 mL) at 0° C. The reaction mixture was stirred overnight at room temperature and washed with saturated ammonium chloride solution (150 mL), water (3×100 mL) and dried over sodium sulfate. Evaporation of the solvents left a red oil that was dissolved in a 1:1 mixture of MeOH and acetone. Concentration and cooling to −30° C. gave 5.78 g (42.1%) of the title compound as slightly yellow crystals. The first crop consisted exclusively of the racemic diastereomer. EIMS (calcd/found): m/e 548.2962/548.2958. Mp: 92-94° C. 1H NMR (CDCl3, δ): 7.22-7.14 (m, 6H); 6.98 (td, 3J=7.3 Hz, 4J=1.4 Hz, 2H); 5.85 (s, 2H); 3.99 (s, 2H); 0.97 (s, 18H); 0.34 (s, 6H); 0.28 (s, 6H); −0.23 (s, 6H). 13C NMR (CDCl3, δ): 164.96; 144.44; 137.55; 125.13; 122.75; 121.41; 118.83; 104.00; 43.06; 25.77; 18.20; 4.34; −4.88; −6.99. The oily residue was washed with copiously with cold MeOH (3×50 mL), cold pentane (50 mL) and dried in vacuo to yield 3.47 g (24.8%) of the fairly pure meso diastereomer as a red oil (total yield 66.9%).
Reaction SMILES: CO[C:3]1[CH:30]=[CH:29][C:6]([NH:7][C:8]2[CH:16]=[C:15]([C:17](O)=O)[C:14]([NH:20][C:21]3[CH:26]=[CH:25][C:24](OC)=[CH:23][CH:22]=3)=[CH:13][C:9]=2C(O)=O)=[CH:5][CH:4]=1.[CH3:31][OH:32].[OH2:33]>O.CO>[CH:3]1[CH:4]=[C:5]2[C:31]([C:9]3[C:8]([NH:7][C:6]2=[CH:29][CH:30]=1)=[CH:16][C:15]1[C:17]([C:26]2[C:21]([NH:20][C:14]=1[CH:13]=3)=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:33])=[O:32]
Reactant: COc1ccc(Nc2cc(C(=O)O)c(Nc3ccc(OC)cc3)cc2C(=O)O)cc1
Reactant: O
Reactant: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 85 °C
Reaction time: 5 h
Yield: 26.42 %

Procedure:
Charged to a container were 360 g of 117% polyphosphoric acid and were heated to 85° C. with agitation. At 85-105° C., 60 g of 2,5-di(4-methoxyanilino) terephthalic acid type I prepared according to Example 1 were added over 60-90 minutes and the reaction mixture was allowed to stir 5 hours at 110-115° C. The reaction mixture was then cooled to approximately 90-95° C. and poured slowly into a container containing 900 g of vigorously stirring methanol over ˜15 minutes. The methanol temperature during the drowning was maintained at <35° C. via an ice-water bath under the round bottom flask. The violet methanol-pigment slurry was allowed to stir 1 hour at room temperature and then heated to reflux (68-72° C.) where it was then held for 1 hour. The slurry was allowed to cool to <65° C. and then poured into a container with 1350 g of water. The resulting water/methanol/pigment slurry was held for 3 hours at 60° C. and then filtered. The resulting presscake was washed with water to a pH of 2.9. Approximately 214.3 g presscake were obtained at approximately 26.42% solids, resulting in approximately 56.6 g solids. Approximately 25 g dry basis pigment from the presscake were reslurried in water and methanol to a total of 150 g water and 150 g methanol. The slurry pH was adjusted to approximately 7 with dilute NaOH. The slurry was then transferred to a Parr pressure reactor and 1.5 g 50% NaOH added. The reactor was sealed and held 6 hours at 120-125° C. After allowing the reaction mixture to cool to room temperature, the slurry was transferred to a beaker. At 40-45° C., 2.0 g Dresinate X dissolved in water were added to the stirring slurry. After 30 minutes at 40-45° C., 4 g of calcium chloride dehydrate, dissolved in water, were added to the slurry. After adjusting the total volume to 1 L with water and stirring for approximately 15 minutes at 40-45° C., the pH was adjusted to 4-4.5 with 75% phosphoric acid. After stirring 1 hour at 40-45° C., the slurry was filtered and the resulting presscake washed with water to conductivity free. The presscake was dried to obtain approximately 24 g of violet pigment powder.