Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:29]([O:31]CC)=[CH2:30])CCC.Cl.O>C(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:23][C:22]1[CH:21]=[C:20]2[C:15]([CH:16]=[CH:17][CH:18]=[N:19]2)=[CH:14][C:13]=1[CH:11]([OH:12])[C:8]1[N:6]2[N:7]=[C:2]([C:29](=[O:31])[CH3:30])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1
Reactant: OC(c1cc2cccnc2cc1F)c1cnc2ccc(Cl)nn12
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: [Pd]
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: ClCCl
Product: CC(=O)c1ccc2ncc(C(O)c3cc4cccnc4cc3F)n2n1
Temperature: 100 °C
Reaction time: 8 h
Yield: 97.8 %

Procedure:
A flask was charged with tetrakis-(triphenylphosphine)-palladium (176 mg, 0.15 mmol) under nitrogen. A solution of (6-chloroimidazo[1,2-b]pyridazin-3-yl)(7-fluoroquinolin-6-yl)methanol (500 mg, 1.52 mmol) in CH2Cl2 (20 mL) was added. The system was purged with nitrogen gas three times and tributyl-(1-ethoxy-vinyl)-stannane (0.54 ml, 1.59 mmol) was added. The temperature was increased to 100° C. and stirred overnight. The reaction mixture was cooled to room temperature, 3N HCl was added and the mixture was stirred for additional 4 hrs. Water was added and the mixture was then extracted with EtOAc, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (3% to 10% MeOH in CH2Cl2) to afford 500 mg (yield: 88%) title compound. LCMS (method B): [MH]+=337, tR=1.88 min.
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])=[CH:19][CH:18]=3)=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[CH:31]([NH:34][CH3:35])([CH3:33])[CH3:32]>>[CH:31]([N:34]([CH3:35])[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])=[CH:19][CH:18]=3)=[CH:13][C:11]=2[CH:12]=1)([CH3:33])[CH3:32]
Reactant: CNC(C)C
Reactant: CS(=O)(=O)OCCc1cc2cc(-c3ccc(C(=O)N4CCOCC4)cc3)ccc2o1
Product: CC(C)N(C)CCc1cc2cc(-c3ccc(C(=O)N4CCOCC4)cc3)ccc2o1

Procedure:
The product from Example 23D and isopropyl(methyl)amine were processed as described in Example 1D to provide the titled compound. 1H NMR (300 MHz, CD3OD) δ 7.82 (m, 1H), 7.74 (d, J=8.1, 2H), 7.58 (m, 2H), 7.52 (d, J=8.1 Hz, 2H), 6.81 (s, 1H), 3.3-3.8 (m, 13H), 2.97 (s, 3H), 1.42 (d, 6.3 Hz, 3H), 1.37 (d, 6.3 Hz, 3H); MS (DCI) m/z 407 (M+H)+;
Reaction SMILES: CS(O[CH:6]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH:17]=1)[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])(=O)=O.[CH3:33][O:34][CH2:35][CH2:36][NH2:37].O>C1COCC1>[CH2:26]([O:25][C:23](=[O:24])[NH:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH:6]([NH:37][CH2:36][CH2:35][O:34][CH3:33])[CH2:7][O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[CH:17]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CC(C)(C)[Si](C)(C)OCC(OS(C)(=O)=O)c1cccc(NC(=O)OCc2ccccc2)c1
Reactant: COCCN
Solvent: O
Solvent: C1CCOC1
Product: COCCNC(CO[Si](C)(C)C(C)(C)C)c1cccc(NC(=O)OCc2ccccc2)c1
Temperature: 70 °C
Yield: 29.9 %

Procedure:
1-(3-(Benzyloxycarbonylamino)phenyl)-2-(tert-butyldimethylsilyloxy)ethyl methanesulfonate (3.5 g) was dissolved in dry THF (10 mL) and methoxyethylamine (5.4 g) was added in a sealed tube and heated to 70° C. for 16 hours. Water was added and the reaction mixture extracted with DCM (2×20 mL). The organic phase was separated, dried over Na2SO4 and concentrated to give the crude product, which was purified by column chromatography to give the title compound (1 g, 30%).
Reaction SMILES: [CH:1]([C:3]12[CH2:17][CH:10]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=31)[C:9]1[C:4]2=[CH:5][CH:6]=[CH:7][CH:8]=1)=[O:2].CC(C)=[O:20].OS(O)(=O)=O.O=[Cr](=O)=O.O>CC(C)=O.[O-2].[O-2].[O-2].[Cr+6]>[CH:5]1[C:4]2[C:3]3([C:1]([OH:20])=[O:2])[CH2:17][CH:10]([C:11]4[C:16]3=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:9]=2[CH:8]=[CH:7][CH:6]=1
Reactant: CC(C)=O
Reactant: O=CC12CC(c3ccccc31)c1ccccc12
Agent: O=[Cr](=O)=O
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(O)C12CC(c3ccccc31)c1ccccc12
Temperature: 25 °C
Yield: 80 %

Procedure:
To a cooled solution (0° C.) of 9-formyl-9,10-dihydro-9,10-methanoanthracene (literature preparation: M. Sunagawa, et al.; Chem. Pharm. Bull. Vol. 27 (1979) pp 1806-1812; U.S. Pat. No. 4,224,344 Sunagawa et al., Sumitomo, Ltd.; Sep. 23, 1980; U.S. Pat. No. 4,358,620 Sunagawa et al., Sumitomo, Ltd.; Nov. 9, 1982) (78.5 mmol) in acetone (260 mL) was added Jones reagent (24 mL; 27 g chromium trioxide, 23 mL water diluted up to 100 mL of reagent solution) in portions. The reagent was added until an orange color persists. The reaction, containing a significant amount of reduced chromium salts, was warmed to room temperature. The solvents were removed in vacuo and replaced with water (300 mL) and saturated with sodium chloride. The aqueous phase was extracted with ethyl acetate (3×300 mL). Combined organic extracts were extracted with 2.5N NaOH (3×400 mL). The basic aqueous extracts were acidified with 3N HCl, saturated with sodium chloride, and extracted with ethyl acetate (4×300 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to a white solid. The title compound was formed in 80% yield as a white solid. MS (Cl CH4) m/z 237 (M+1,100), 265 (m+29,10), 219 (22), 209 (15), 193 (20).
Reaction SMILES: [OH:1][C:2]([CH3:8])([CH3:7])[C:3]([O:5][CH3:6])=[O:4].[O:9]1[CH:14]=[CH:13][CH2:12][CH2:11][CH2:10]1.O>ClCCl.CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1>[CH3:7][C:2]([O:1][CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][O:9]1)([CH3:8])[C:3]([O:5][CH3:6])=[O:4]
Reactant: COC(=O)C(C)(C)O
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)C(C)(C)OC1CCCCO1
Reaction time: 1.5 h
Yield: 84.5 %

Procedure:
To a mixture of methyl 2-hydroxy-2-methylpropanoate (5.04 g, 42.7 mmol) and 3,4-dihydro-2H-pyran (5.85 ml, 64.0 mmol) in dichloromethane (40 ml) was added pyridine 4-methylbenzenesulfonate (0.536 g, 2.13 mmol) and the reaction mixture was stirred for 1.5 hours. The reaction mixture was poured into water and extracted with Et2O. The organic layers were dried over Na2SO4 filtered, and concentrated in vacuo to give a crude oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 100:0 to 17:3) to afford methyl 2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propanoate (7.30 g, 36.1 mmol, 85% yield) as a colorless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35 (s, 3 H) 1.36-1.55 (m, 7 H) 1.57-1.81 (m, 2 H) 3.32-3.42 (m, 1 H) 3.62 (s, 3 H) 3.72-3.85 (m, 1 H) 4.65-4.75 (m, 1 H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[O:8][C:6](=O)[C:5]2=[CH:11][C:12]=1[Cl:13].Cl.[Cl:15][CH2:16][CH2:17][NH2:18]>>[Cl:13][C:12]1[CH:11]=[C:5]2[C:6](=[O:8])[N:18]([CH2:17][CH2:16][Cl:15])[C:9](=[O:10])[C:4]2=[CH:3][C:2]=1[Cl:1]
Reactant: NCCCl
Reactant: O=C1OC(=O)c2cc(Cl)c(Cl)cc21
Agent: Cl
Product: O=C1c2cc(Cl)c(Cl)cc2C(=O)N1CCCl
Yield: 58 %

Procedure:
The compound was prepared as described in example 5A, starting from 14 g (0.065 mole) of 4,5-dichlorophthalic anhydride (Beilstein 4thEd. vol. 17 System No 6143) and 7.51 g (0.065 mole) of 2-chloroethylamine monohydrochloride. 10.5 g of the title product were obtained; mp=144°-145° C. (ethyl acetate)
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:22]3[CH2:21][CH2:20][CH2:19][C:18]=3[CH:17]=[C:16]3[C:12]=2[CH2:13][CH:14]([CH3:24])[C:15]3=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>C(OCC)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:12]3[CH2:13][C:14]([CH3:24])=[CH:15][C:16]=3[CH:17]=[C:18]3[C:22]=2[CH2:21][CH2:20][CH2:19]3)=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC1Cc2c(cc3c(c2-c2ccc(C(C)(C)C)cc2)CCC3)C1=O
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CC1=Cc2cc3c(c(-c4ccc(C(C)(C)C)cc4)c2C1)CCC3
Temperature: 25 °C
Reaction time: 1 h

Procedure:
10 g (0.031 mol) of 4-(4-tert-butylphenyl)-2-methyl-3,5,6,7-tetrahydro-s-indacen-1(2H)-one (1c) were added dropwise at 0° C. to a solution of 0.6 g (0.016 mol) of lithium aluminum hydride in 100 ml of diethyl ether. The reaction mixture obtained was warmed to room temperature and stirred for a further one hour. 50 ml of 5% strength hydrochloric acid were added. The organic phase was separated off, washed twice with water and dried over magnesium sulfate. The residue was dissolved in 200 ml of benzene and, after addition of 0.5 g of p-toluenesulfonic acid, refluxed for 15 minutes. The solution was cooled to room temperature, washed with a 5% strength solution of sodium hydrogencarbonate and dried over magnesium sulfate. Evaporation of the solvent gave pure 4-(4-tert-butylphenyl)-6-methyl-1,2,3,5-tetrahydro-s-indacene in quantitative yield.
Reaction SMILES: [CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([C:25]1([NH:31][CH2:32][CH2:33][OH:34])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)#[CH:24]>>[CH2:1]([C:8]1[C:13]([C:24]#[C:23][C:25]2([NH:31][CH2:32][CH2:33][OH:34])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CO[C@@H]1CN(c2ccc(I)c(Cc3ccccc3)n2)C[C@H]1O
Reactant: C#CC1(NCCO)CCCCC1
Product: CO[C@@H]1CN(c2ccc(C#CC3(NCCO)CCCCC3)c(Cc3ccccc3)n2)C[C@H]1O

Procedure:
This was synthesized in the same manner as in Example 6 except that 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine (Production Example 1) and 2-[(1-ethynylcyclohexyl)amino]ethanol (Production Example 20) were used.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17](O)=[O:18].FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>>[Br:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([O:9][CH3:10])[CH:5]=1)=[O:18]
Reactant: O=C(O)CCCCCBr
Reactant: COc1ccccc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: COc1ccc(C(=O)CCCCCBr)cc1OC
Temperature: 25 °C
Reaction time: 17 h
Yield: 65.1 %

Procedure:
A mixture of 1.0 mL (7.8 mmol) of 1,2-dimethoxybenzene and 2.0 g (10 mmol) of 6-bromohexanoic acid was warmed briefly until homogeneous and stirred while 1.7 mL (11.7 mmol) of trifluoroacetic anhydride was added. The reaction mixture was stirred at room temperature for 17 hours and then was poured into sodium bicarbonate solution. The product was extracted with ethyl acetate and the dried extract was concentrated to an oil which was purified by chromatography on 150 g of silica gel. Elution with 25% ethyl acetate-hexane gave 1.6 g (65% yield) of 1-(6-bromo-1-oxohexyl)-3,4-dimethoxybenzene. The nmr spectrum was consistent with the structure.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([NH2:11])[CH2:8][CH2:9][CH3:10].[CH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][C:13]=1[O:22][CH2:23][CH2:24][CH2:25][CH2:26]Cl>CS(C)=O.O>[CH2:7]([NH:11][CH2:26][CH2:25][CH2:24][CH2:23][O:22][C:13]1[CH:14]=[CH:15][C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=1)[CH2:8][CH2:9][CH3:10]
Reactant: ClCCCCOc1ccc2ccccc2c1
Reactant: CCCCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCNCCCCOc1ccc2ccccc2c1
Temperature: 140 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and n-butylamine (0.32 ml, 0.003 mole) was taken in dry DMSO (40 ml). Now 4-(2-naphthyloxy)-1-chlorobutane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 140° C. for 8 hrs and the reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to oily compound which was later crystallized by benzene hexane to get N-(n-butyl)-(4-(naphthalen-2-yloxy)butyl)amine, solid. m.p. oil, (yield 0.56 gm, 96.5%).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]([NH:38][CH3:39])[CH2:6][S:7][CH2:8][C:9]1[C:27]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])=[CH:26][C:25]([O:36][CH3:37])=[CH:24][C:10]=1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)=[O:12])=[O:4].[C:40]([O:59][CH2:60][CH2:61][C:62](Cl)=[O:63])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(N(CC)CC)C>C(Cl)Cl>[Si:29]([O:28][C:27]1[C:9]([CH2:8][S:7][CH2:6][C@H:5]([N:38]([C:62](=[O:63])[CH2:61][CH2:60][O:59][C:40]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH3:39])[C:3]([O:2][CH3:1])=[O:4])=[C:10]([CH:24]=[C:25]([O:36][CH3:37])[CH:26]=1)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)=[O:12])([C:32]([CH3:34])([CH3:35])[CH3:33])([CH3:31])[CH3:30]
Reactant: O=C(Cl)CCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CN[C@@H](CSCc1c(O[Si](C)(C)C(C)(C)C)cc(OC)cc1C(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)OC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](CSCc1c(O[Si](C)(C)C(C)(C)C)cc(OC)cc1C(=O)OCc1ccc([N+](=O)[O-])cc1)N(C)C(=O)CCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 65.8 %

Procedure:
A solution of 0.64 g of p-nitrobenzyl (R)-2-[[[2-(methoxycarbonyl)-2-(methylamino)-ethyl]thio]methyl]-3-(tert-butyldimethylsilyloxy)-5-methoxybenzoate and 0.58 g of 3-trityloxypropionyl chloride in 6 ml of methylene chloride was treated at 0° C. with 0.17 g of triethylamine. The mixture was stirred at 0° C. for 30 minutes, then diluted with methylene chloride, and washed successively with 5% sodium bicarbonate solution and brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated in vacuo. The residual oil was chromatographed on silica gel using ethyl acetate/hexane (1:2, v/v) as eluent to yield 0.65 g of p-nitrobenzyl (R)-3-(tert-butyldimethylsilyloxy)-5-methoxy-2-[[[2-(3-trityloxypropionyl-methylamino)-2-methoxycarbonyl-ethyl]thio]methyl]-benzoate as an oil.
Reaction SMILES: F[C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O>[N:14]1([C:2]2[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=2[CH:4]=[O:5])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1
Reactant: C1COCCN1
Reactant: O=Cc1ccc(C(F)(F)F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: O=Cc1ccc(C(F)(F)F)cc1N1CCOCC1
Temperature: 100 °C
Reaction time: 8 h
Yield: 41.3 %

Procedure:
A 100 mL round-bottom flask was charged with 2-fluoro-4-(trifluoromethyl)benzaldehyde (1.90 g, 9.89 mmol, 1.00 equiv), morpholine (1.30 g, 14.9 mmol, 1.51 equiv), potassium carbonate (3.45 g, 25.0 mmol, 2.52 equiv), and dimethyl sulfoxide (20 mL). The resulting solution was stirred overnight at 100° C. in an oil bath and diluted with H2O (30 mL). The resulting solution was extracted with dichloromethane (2×20 mL) and the organic layers were combined, washed with H2O (3×20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/5) to yield 1.06 g (41% yield) of 2-(morpholin-4-yl)-4-(trifluoromethyl)benzaldehyde as yellow oil. LCMS (ESI, m/z): 260 [M+H]+.
Reaction SMILES: [CH2:1]([CH:3]([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:4][C:5]1[CH:6]=[C:7]2[C:28]3[CH:27]=[CH:26][S:25][C:24]=3[C:20]3[S:21][CH:22]=[CH:23][C:19]=3[C:8]2=[CH:9][C:10]=1[CH2:11][CH:12]([CH2:17][CH3:18])[CH2:13][CH2:14][CH2:15][CH3:16])[CH3:2].C([Li])(C)(C)C.[CH3:38][Sn:39](Cl)([CH3:41])[CH3:40]>C(OCC)C>[CH2:1]([CH:3]([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:4][C:5]1[CH:6]=[C:7]2[C:28]3[CH:27]=[C:26]([Sn:39]([CH3:41])([CH3:40])[CH3:38])[S:25][C:24]=3[C:20]3[S:21][C:22]([Sn:39]([CH3:41])([CH3:40])[CH3:38])=[CH:23][C:19]=3[C:8]2=[CH:9][C:10]=1[CH2:11][CH:12]([CH2:17][CH3:18])[CH2:13][CH2:14][CH2:15][CH3:16])[CH3:2]
Reactant: CCCCC(CC)Cc1cc2c(cc1CC(CC)CCCC)c1ccsc1c1sccc21
Reactant: C[Sn](C)(C)Cl
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Product: CCCCC(CC)Cc1cc2c(cc1CC(CC)CCCC)c1cc([Sn](C)(C)C)sc1c1sc([Sn](C)(C)C)cc21
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 84 %

Procedure:
A dry 100-mL three-neck flask was flushed with N2 and was charged with 5,6-bis(2-ethylhexyl)naphtho[2,1-b:3,4-b′]dithiophene (0.50 g, 1.1 mmol) and diethyl ether (Et2O) (11 mL, 0.10 M) via deoxygenated syringe. The reaction flask was cooled to −78° C. and a 1.3 M solution of tert-butyllithium in hexanes (2.3 mL, 3.0 mmol) was added drop-wise via deoxygenated syringe. After 30 minutes of stirring at −78° C., the solution was chilled to 0° C. and stirring was continued for 5 minutes, at which point the reaction mixture was cooled back to −78° C. A 1 M solution of trimethyltin chloride (4.4 mL, 4.4 mmol) in hexanes was added to the reaction flask drop-wise and stirring continued for 30 minutes at −76° C. The cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature. As the reaction was completed, cool DI water (10 mL) was slowly added to the reaction flask. Then, the reaction mixture was poured into 50 mL of cool water and extracted with MTBE (100 mL) three times. The combined organic layer was washed with water two times and dried over anhydrous magnesium sulfate (MgSO4). After the product was filtered, the solvent was removed by rotary evaporation. The crude product was purified by precipitation into methanol from a THF solution to yield pale yellow oil (0.73 g, 84%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[S:20][C:16]=3[C:15]([S:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[C:14]3[C:9]=2[CH:10]=[CH:11][CH:12]=[CH:13]3)[CH:5]=[C:4]([Br:32])[C:3]=1[OH:33].O[C@@H:35]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:36]([O:38]C)=[O:37].BrBr>>[Br:32][C:4]1[CH:5]=[C:6]([C:8]2[C:17]3[C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[S:20][C:16]=3[C:15]([S:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[C:14]3[C:9]=2[CH:10]=[CH:11][CH:12]=[CH:13]3)[CH:7]=[C:2]([Br:1])[C:3]=1[O:33][C@H:35]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:36]([OH:38])=[O:37]
Reactant: COC(=O)[C@@H](O)Cc1ccccc1
Reactant: Oc1c(Br)cc(-c2c3ccccc3c(Sc3ccccc3)c3sc4ccccc4c23)cc1Br
Agent: BrBr
Product: O=C(O)[C@@H](Cc1ccccc1)Oc1c(Br)cc(-c2c3ccccc3c(Sc3ccccc3)c3sc4ccccc4c23)cc1Br

Procedure:
Prepared from of 2,6-dibromo-4-(6-phenylsulfanyl-benzo[b]naphtho[2,3-d ]thiophen-11-yl)-phenol (Example 64) and (S)-2-hydroxy-3-phenylpropionic acid, methyl ester (Example 96). White solid: NMR (DMSO-d6); δ8.50 (d, J=8 Hz, 1 H), 7.98 (d, J=8 Hz, 1 H), 7.83 (d, J=2 Hz, 1 H), 7.81 (d, J=2 Hz, 1 H),7.71 (ddd, J=6, 5, 2 Hz, 2 H), 7.58 (m, 2 H), 7.47 (ddd, J=8, 8, 1 Hz, 1 H), 7.42 (d, J=8 Hz, 2 H), 7.34 (t, J=7 Hz, 2 H), 7.29-7.20 (m, 4 H), 7.17-7.08 (m, 3 H), 6.67 (d, J=8 Hz, 1 H), 5.35 (t, J=7 Hz, 1 H, CH), 3.41 (d, J=7 Hz, 2 H); MS (+FAB): [M+], 2 bromine isotope pattern, 738 (35%), 740 (90%) 742 (60%); Anal. Calc. for C37H24Br203S2: C, 60.01, H, 3.27, N, 0.00. Found: C, 58.57, H, 3.04, N, 0.22.
Reaction SMILES: Br[C:2]1[S:6][C:5](/[CH:7]=[CH:8]/[C:9]([O:11][CH2:12]C)=[O:10])=[CH:4][CH:3]=1.B([O-])([O-])O[C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O>[CH:22]([C:19]1[CH:20]=[CH:21][C:16]([C:2]2[S:6][C:5](/[CH:7]=[CH:8]/[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=2)=[CH:17][CH:18]=1)([CH3:24])[CH3:23]
Reactant: CCOC(=O)/C=C/c1ccc(Br)s1
Reactant: CC(C)c1ccc(OB([O-])[O-])cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: COC(=O)/C=C/c1ccc(-c2ccc(C(C)C)cc2)s1
Temperature: 25 °C
Yield: 75.7 %

Procedure:
Under argon atmosphere, a solution of ethyl (E)-3-(5-bromothiophen-2-yl)acrylate (1.00 g), 4-isopropylphenyl borate (0.86 g) and potassium carbonate (1.12 g) in toluene/ethanol/water (40/4/4 ml) was stirred at room temperature for 1 hour. To the mixture was added tetrakistriphenylphosphine palladium (0.14 g), and the mixture was refluxed for 18 hours and then cooled to room temperature. The organic layer was washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the mixture was concentrated, and the residue was purified with column chromatography (ethyl acetate/hexane=1:9) to give pale yellow crystals of methyl (E)-3-[5-(4-isopropylphenyl)-thiophen-2-yl]acrylate (0.83 g).
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[Li]CCCC.CN([CH:23]=[O:24])C.[NH4+].[Cl-]>CCOCC>[CH:3]1[C:4]2[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[S:6][C:5]=2[CH:13]=[CH:14][C:2]=1[CH:23]=[O:24]
Reactant: CN(C)C=O
Reactant: Brc1ccc2sc3ccccc3c2c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Product: O=Cc1ccc2sc3ccccc3c2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A cooled (0° C.) suspension of commercially available 2-bromodibenzo[b,d]thiophene (500 mg; 1.90 mmol) in anh. Et2O (5 ml), under nitrogen, was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (1.26 ml; 2.01 mmol). The resulting suspension was further stirred at 0° C. for 30 min. Anh. DMF (0.156 ml; 2.03 mmol) was then added, and the mixture was stirred at rt for 20 min. Aq. sat. NH4Cl and Et2O were successively added, and the aq. layer was further extracted with Et2O. The mixed organic layers were washed with water, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM) afforded dibenzo[b,d]thiophene-2-carbaldehyde as an off-white solid. LC-MS (conditions A): tR=0.87 min.; no ionisation.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH2:9])=[C:4]([NH2:10])[CH:3]=1.[CH:11]1([N:14]=[C:15]=S)[CH2:13][CH2:12]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C[N+]1(CCN=C=NC2CCCCC2)CCOCC1>N1C=CC=CC=1>[CH:11]1([NH:14][C:15]2[NH:9][C:5]3[CH:6]=[C:7]([Cl:8])[C:2]([Cl:1])=[CH:3][C:4]=3[N:10]=2)[CH2:13][CH2:12]1
Reactant: S=C=NC1CC1
Reactant: Nc1cc(Cl)c(Cl)cc1N
Agent: C[N+]1(CCN=C=NC2CCCCC2)CCOCC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: c1ccncc1
Product: Clc1cc2nc(NC3CC3)[nH]c2cc1Cl
Yield: 70.5 %

Procedure:
4,5-Dichloro-1,2-phenylenediamine (6.04 g, 34.1 mmol), cyclopropyl isothiocyanate (3.69 g, 37.2 mmol), 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (20.1 g, 47.4 mmol) and pyridine (135 mL) were used according to general procedure I. The product was recrystallized from acetonitrile to afford 5.82 g (70%) of a yellow solid; m.p. 223-225° C. Anal. Calcd for C10H9Cl2N3 : C, 49.61; H, 3.75; N, 17.36. Found: C, 49.53; H, 3.78; N, 17.12.