Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:10]([CH3:12])([CH3:11])[CH2:9][CH2:8][C:7]1=[O:13])=[O:5])[CH3:2].C[Si](C)(C)N[Si](C)(C)C.[Li].[C:24]([C:28]1[CH:29]=[C:30]([CH:33]=[C:34]([C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]=1[O:36][Si](C)(C)C)[CH:31]=O)([CH3:27])([CH3:26])[CH3:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[C:10]([CH3:12])([CH3:11])[CH2:9][C:8](=[CH:31][C:30]2[CH:29]=[C:28]([C:24]([CH3:25])([CH3:27])[CH3:26])[C:35]([OH:36])=[C:34]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:33]=2)[C:7]1=[O:13])=[O:5])[CH3:2]
Reactant: CC(C)(C)c1cc(C=O)cc(C(C)(C)C)c1O[Si](C)(C)C
Reactant: CCOC(=O)N1C(=O)CCC1(C)C
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Li]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOC(=O)N1C(=O)C(=Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)CC1(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a chilled solution (-70° C.) of 1.657 g (8.95 mmol) of the thus obtained 1-ethoxycarbonyl-5,5-dimethylpyrrolidin-2-one in THF (45 ml) was added 9 ml of a THF solution of 1.0M lithium hexamethydisilazane under a nitrogen atmosphere. Five minutes later, 2.74 g (9 mmol) of 3,5-di-tert-butyl-4-trimethylsiloxybenzaldehyde was added thereto and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into ice-water and extracted with dichloromethane. The dichloromethane layer was washed with water, dried over magnesium sulfate and evaporated to give a residue, which was then dissolved in 40 ml of toluene and combined with 280 mg of p-toluenesulfonic acid and the mixture was refluxed for 1.5 hours. After cooled down, the reaction mixture was evaporated and the resulting residue was dissolved in 30 ml of THF. Under ice-cooling, 3.5 ml of a THF solution of 2.0M tetra-n-butylammonium fluoride was added thereto and the mixture was stirred for 10 minutes. The mixture was poured into ice-water containing sodium bicarbonate and extracted with dichloromethane. The dichloromethane layer was washed with an aq. sodium bicarbonate, water, then saturated brine and dried over magnesium sulfate and evaporated to give 1-ethoxycarbonyl-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)-5,5-dimethylpyrrolidin-2-one as residue, which was then dissolved in a methanol/water (4/1) mixed solution (100 ml). Five % solution of potassium hydroxide (5 ml) was added thereto while being stirred under ice-cooling and stirred at room temperature for 3.5 hours. The reaction mixture was neutralized with 38 ml of 2N hydrochloric acid and extracted with dichloromethane. The organic layer was washed with saturated brine, dried over magnesium sulfate and evaporated to give a residue, which was recrystallized from a dichloromethane/ether mixture to give 386 mg of the objective compound. Then the mother liquor was chromatographed on silica gel (toluene/ethyl acetate=1/1) and recrystallized to give 559 mg of the objective compound. Totally, 945 mg of the objective compound was obtained in 24% overall yield.
Reaction SMILES: [F:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[Br:12]Br.Br>C(Cl)(Cl)(Cl)Cl>[Br:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([F:1])=[CH:3][CH:4]=1
Reactant: Fc1cccc2ccccc12
Reactant: BrBr
Agent: Br
Solvent: ClC(Cl)(Cl)Cl
Product: Fc1ccc(Br)c2ccccc12
Reaction time: 2 h

Procedure:
To a 50 mL round-bottomed flask equipped with condenser and N2 inlet were added 3.75 mL (5.0 g, 34.25 mmol) 1-fluoronaphthalene and 10 mL carbon tetrachloride, followed by dropwise addition of 1.7 mL (5.5 g., 34.375 mmol) bromine over 3 min. The reaction was heated to 50-60° C. as HBr was evolved for 2 hour, then cooled and concentrated. The residue was dissolved in methanol and kept overnight at 0° C. After filtration with cold methanol, the product, with melting point close to room temperature, was 4.62 g (60%) of a yellow oil. 1H-NMR (δ, CDCl3): 7.02 (t, J=8, 1H), 7.6-7.7 (m, 3H), 8.10 (d, J=8.5, 1H), 8.20 (d, J=8.5, 1H); GCMS (%): 224/226 (parent, Br79/Br81 100).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].[CH3:13][Si:14]([CH2:17][CH2:18][O:19][CH2:20]Cl)([CH3:16])[CH3:15]>O.CC(OC)(C)C>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([CH2:20][O:19][CH2:18][CH2:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Clc1ncnc2[nH]ccc12
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: O
Product: C[Si](C)(C)CCOCn1ccc2c(Cl)ncnc21
Temperature: -5 °C
Reaction time: 0.25 h
Yield: 88.9 %

Procedure:
To a flask equipped with a nitrogen inlet, addition funnel, thermowell, and mechanical stirrer was added 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 600 g, 3.91 mol) and dimethylacetimide (9.6 L). The mixture was cooled to −5° C. in an ice/brine bath and sodium hydride (NaH, 60 wt %, 174 g, 4.35 mol, 1.1 equiv) was added in portions as a solid. The mixture went to a dark solution during 15 minutes and trimethylsilylethoxymethyl chloride (2, 763 mL, 4.31 mol, 1.1 equiv) was added slowly via an addition funnel at a rate that the temperature did not exceed 5° C. The reaction was stirred for 30 minutes, determined to be complete by TLC and HPLC, and water (1 L) was slowly added to quench the reaction. The mixture was then diluted with water (12 L) and MTBE (8 L). The layers were separated and the aqueous was re-extracted with MTBE (8 L). The combined organic layers were washed with water (2×4 L) and brine (4 L), dried over sodium sulfate (NaSO4), and solvents removed under reduced pressure. The residue was dissolved in heptane (2 L), filtered and loaded onto a silica gel (3.5 kg) column eluting with heptane (˜6 L), 95% heptane/ethyl acetate (˜12 L), 90% heptane/ethyl acetate (10 L), and finally 80% heptane/ethyl acetate (10 L). The pure fractions were combined and concentrated under reduced pressure to give 4-chloro-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine (3a, 987 g, 1109.8 g theoretical, 88.9% yield) as a pale yellow oil that partially solidified to an oily solid on standing at room temperature. For 3a: 1H NMR (DMSO-d6, 300 MHz) δ ppm 8.67 (s, 1H), 7.87 (d, 1H, J=3.8 Hz), 6.71 (d, 1H, J=3.6 Hz), 5.63 (s, 2H), 3.50 (t, 2H, J=7.9 Hz), 0.80 (t, 2H, J=8.1 Hz), 1.24 (s, 9H); 13C NMR (DMSO-d6, 100 MHz) δ ppm 151.3, 150.8, 150.7, 131.5, 116.9, 99.3, 72.9, 65.8, 17.1, −1.48; C12H18ClN3OSi (MW 283.83), LCMS (EI) m/e 284/286 (M++H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: C1COCCN1
Reactant: Clc1nc(Cl)c2sccc2n1
Solvent: CO
Product: Clc1nc(N2CCOCC2)c2sccc2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
A mixture of 2,4-dichloro-thieno[3,2-d]pyrimidine (VIII), (8.68 g, 42.34 mmol), morpholine (8.11 mL, 2.2 eq.) and MeOH (150 mL) was stirred at room temperature for 1 h. The reaction mixture was then filtered, washed with water and MeOH, to yield the title compound as a white solid (11.04 g, 100%).
Reaction SMILES: [CH3:1][CH:2]([CH3:33])[CH2:3][C@@H:4]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[CH:5]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].[CH2:34](Br)[CH:35]=[CH2:36]>>[CH3:1][CH:2]([CH3:33])[CH2:3][C@@H:4]([C:23]([O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:24])[C:5]([CH2:36][CH:35]=[CH2:34])([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]
Reactant: C=CCBr
Reactant: CC(C)C[C@@H](C(=O)OCc1ccccc1)C(C(=O)OCc1ccccc1)C(=O)OC(C)(C)C
Product: C=CCC(C(=O)OCc1ccccc1)(C(=O)OC(C)(C)C)[C@@H](CC(C)C)C(=O)OCc1ccccc1
Yield: 91.3 %

Procedure:
In a manner analogous to that described in Example 45(i), from 7.28 g of 1,2-dibenzyl 1-tert.butyl 4-methyl-1,1,2(R)-pentanetricarboxylate and 3.88 g of allyl bromide there were obtained 7.234 g of 1,2-dibenzyl 1-tert.butyl 4-methyl-1-(prop-2-en-1-yl)-1,1,2(R)-pentanetricarboxylate in the form of a colorless oil; MS: 495 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[C:7]([NH2:16])[CH:8]=[C:9]([O:14][CH3:15])[C:10]=2[O:12][CH3:13])[N:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:24]1(=[O:41])[N:28]([CH2:29][CH2:30][CH2:31][CH:32](I)[CH2:33][CH3:34])[C:27](=[O:36])[C:26]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:25]12.C(Cl)(Cl)[Cl:43]>C(OCCO)C>[ClH:43].[CH3:13][O:12][C:10]1[C:9]([O:14][CH3:15])=[CH:8][C:7]([NH:16][CH:32]([CH2:33][CH3:34])[CH2:31][CH2:30][CH2:29][N:28]2[C:24](=[O:41])[C:25]3=[CH:40][CH:39]=[CH:38][CH:37]=[C:26]3[C:27]2=[O:36])=[C:6]2[C:11]=1[C:2]([CH3:1])=[CH:3][CH:4]=[N:5]2
Reactant: COc1cc(N)c2nccc(C)c2c1OC
Reactant: CCC(I)CCCN1C(=O)c2ccccc2C1=O
Reactant: ClC(Cl)Cl
Solvent: CCOCCO
Solvent: CCN(CC)CC
Product: CCC(CCCN1C(=O)c2ccccc2C1=O)Nc1cc(OC)c(OC)c2c(C)ccnc12
Product: Cl
Reaction time: 8 h
Yield: 63 %

Procedure:
A solution of 4-methyl-5,6-dimethoxy-8-aminoquinoline (0.042 mole) in 2-ethoxyethanol (21 ml) containing triethylamine (5.8 ml) and 1-phthalimido-4-iodohexane (14.9 g, 0.042 mole) was heated at 110° for 2.5 hr. Thereafter, there were two incremental additions of triethylamine and side-chain over 6 hrs, and the heating at 110° continued overnight. Th reaction mixture was diluted with chloroform and washed with water (×2). The organic layer was dried (K2CO3) and the solvents were removed in vacuo. The residue was dissolved in ether, filtered and acidified with excess ethereal HCl. The red gum which separated was crystallized from ethanol (150 ml) to yield 5,6-dimethoxy-4-methyl-8-(4-phthalimido-1-ethylbutylamino)quinoline hydrochloride (13 g, 63%), mp 163°-166°.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](Cl)=[O:11])=[CH:5][CH:4]=1.[CH:13]([NH2:15])=[O:14].N1C=CC=CC=1.C[C:23](C)=[O:24]>CCOC(C)=O>[CH:13]([NH:15][C:10](=[O:11])[CH2:9][C:6]1[CH:5]=[CH:4][CH:3]=[C:8]([O:24][CH3:23])[CH:7]=1)=[O:14]
Reactant: CC(C)=O
Reactant: NC=O
Reactant: COc1ccc(CC(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: COc1cccc(CC(=O)NC=O)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a stirring solution of (4-methoxyphenyl)acetyl chloride (0.500 g, 2.71 mmol) in acetone (1.0 mL) at 0° C. was added a solution of formamide (0.28 mL, 7.0 mmol) and pyridine (0.28 mL, 3.5 mmol) in acetone (1.0 mL). The resulting solution was stirred at 0° C. for 30 min and then overnight at rt. The reaction mixture was diluted with EtOAc and washed with 1M HCl, sat. NaHCO3 solution, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography eluting with 1% MeOH in DCM yielding the title compound as an off-white solid. MS (ES+): m/z=194.11 [MH+]. HPLC: tR=2.57 min (ZQ3, polar—5 min).
Reaction SMILES: [NH:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]3[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[C:23]([O:30][CH3:31])[CH:22]=3)[CH:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:32][C:33]1[C:38]([O:39][CH3:40])=[CH:37][C:36]([C:41]2[CH:46]=[C:45]([CH2:47]Cl)[CH:44]=[CH:43][N:42]=2)=[CH:35][C:34]=1[O:49][CH3:50]>>[ClH:29].[ClH:32].[ClH:29].[Cl:29][C:24]1[C:23]([O:30][CH3:31])=[CH:22][C:21]([C:17]2[CH:16]=[C:15]([CH2:14][N:11]3[CH2:12][CH2:13][CH:8]([N:1]([CH2:47][C:45]4[CH:44]=[CH:43][N:42]=[C:41]([C:36]5[CH:37]=[C:38]([O:39][CH3:40])[C:33]([Cl:32])=[C:34]([O:49][CH3:50])[CH:35]=5)[CH:46]=4)[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:9][CH2:10]3)[CH:20]=[CH:19][N:18]=2)=[CH:26][C:25]=1[O:27][CH3:28]
Reactant: COc1cc(-c2cc(CN3CCC(Nc4ccccc4)CC3)ccn2)cc(OC)c1Cl
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1Cl
Product: COc1cc(-c2cc(CN3CCC(N(Cc4ccnc(-c5cc(OC)c(Cl)c(OC)c5)c4)c4ccccc4)CC3)ccn2)cc(OC)c1Cl
Product: Cl

Procedure:
4-Anilino-1-[[2-(4-chloro-3,5-dimethoxyphenyl)pyridin-4-yl]methyl]piperidine (230 mg) and 2-(4-chloro-3,5-dimethoxyphenyl)-4-chloromethylpyridine (157 mg) were condensed in the same manner as described in Example 9. The title compound was obtained as yellow powder after converting a free base to a trihydrochloride.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.C(OC(=O)C)(=O)C.C([O-])(=O)C.[K+].[N:22](OCCC(C)C)=O>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:7][CH:8]=1)[NH:6][N:22]=[CH:9]2
Reactant: CC(C)CCON=O
Reactant: Cc1cc(Br)ccc1N
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)=O
Solvent: ClC(Cl)Cl
Product: Brc1ccc2[nH]ncc2c1
Temperature: 68 °C
Reaction time: 0.83 h
Yield: 94 %

Procedure:
A flask containing 4-bromo-2-methylaniline (95.0 g) in chloroform (0.70 L) was treated with acetic anhydride (0.109 L) at <40° C. The solution was stirred for 50 minutes and potassium acetate (14.6 g) and isoamyl nitrite (0.147 L) was charged. The solution was refluxed at 68° C. for 20 h. The temperature was cooled to 25° C. and the volatiles distilled at 30 mmHg vacuum (T=30-40° C.). Once most of the solvents had distilled, a total of 225 mL of water was charged in portions and the azeotrope of water and the various volatiles distilled. The product mass was transferred back into the reaction vessel using water (50 mL) and concentrated hydrochloric acid (400 mL) charged. The mixture was heated to 50-55° C. and another 100 mL acid charged in portions over 2 h. The solution was cooled to 20° C. and 50% sodium hydroxide (520 g) was charged at <37° C. to bring the pH to 11. Water (100 mL) and ethyl acetate (350 mL) was added and the mixture filtered through a Celite pad. The layers were separated and the aqueous phase further extracted with ethyl acetate (2×200 mL). The combined organic layers were mixed with brine (240 mL), filtered through a Celite pad and separated. The organic solution was dried over magnesium sulfate (3 g) and filtered through a silica gel pad (45 g) with ethyl acetate. The eluant was concentrated by rotary evaporation, adding a total of 0.45 L of heptane during the distillation and continueing until only dry solids remain. The solids were slurried with heptane (0.1 L), filtered and dried under vacuum at 45° C. to produce 91.9 g of 5-bromoindazole (94% yield).
Reaction SMILES: C(C1C=[C:7]([CH2:16][CH2:17][C:18]2[CH:23]=[C:22](C(C)(C)C)[C:21]([OH:28])=[C:20](C(C)(C)C)[CH:19]=2)[CH:8]=[C:9]([C:12]([CH3:15])(C)C)C=1O)(C)(C)C.[CH2:33]1C2C(=CC=CC=2)CCC1.[OH2:43]>C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:33][CH:17]([C:18]1[CH:19]=[CH:20][C:21]([OH:28])=[CH:22][CH:23]=1)[C:16]1[CH:7]=[CH:8][C:9]([OH:43])=[CH:12][CH:15]=1
Reactant: c1ccc2c(c1)CCCC2
Reactant: CC(C)(C)c1cc(CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Reactant: O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CC(c1ccc(O)cc1)c1ccc(O)cc1
Yield: 97 %

Procedure:
A solution of 5.0 grams (0.011 mole) of 1,2-bis(3,5-di-t-butyl-4-hydroxyphenyl)ethane dissolved in 30 milliliters of tetralin containing 0.2 gram (0.0012 mole) of p-toluensulfonic acid was heated to reflux for a total of 3 hours. The reaction mixture was cooled and poured into 50 milliliters of water. The precipitated solid was collected by suction filtration and recrystallized from ethanol to yield 2.3 grams (97 percent) of bisphenol E, melting point 199°-200° C.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]1([OH:7])[CH2:6][CH2:5][CH2:4]1.N1C=CC=CC=1.Cl[C:17]([O:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)=[O:18]>ClCCl>[F:1][C:2]([F:9])([F:8])[C:3]1([O:7][C:17](=[O:18])[O:19][C:20]2[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: OC1(C(F)(F)F)CCC1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Oc1ccc([N+](=O)[O-])cc1)OC1(C(F)(F)F)CCC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 48.1 %

Procedure:
To 1-trifluoromethyl-cyclobutanol (2.2 g, 15 mmol) in dichloromethane (7.5 mL, 2M) was added pyridine (3 mL) and 4-nitrophenyl chloroformate (4 g, 18.3 mmol). The flask was sealed and stirred at room temperature for 2 days. The reaction was diluted with dichloromethane (50 mL) and washed with 1M KHSO4(aq), saturated sodium bicarbonate, water, and brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (gradient elution with 10% to 40% EtOAc in hexane) gave 2.2 g (48% yield) of carbonic acid 4-nitro-phenyl ester 1-trifluoromethyl-cyclobutyl ester as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 8.35 (d, 2H), 7.50 (d, 1H), 2.78-2.85 (m, 2H), 2.58-2.70 (m, 2H), 1.9-2.1 (m, 2H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([F:36])([F:35])[C:25]([F:34])([F:33])[C:26]([F:32])([F:31])[C:27]([F:30])([F:29])[F:28].[P:37]([O:44]CC)([O:41][CH2:42][CH3:43])[O:38][CH2:39][CH3:40]>>[CH2:39]([O:38][P:37]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([F:36])([F:35])[C:25]([F:34])([F:33])[C:26]([F:32])([F:31])[C:27]([F:30])([F:29])[F:28])([O:41][CH2:42][CH3:43])=[O:44])[CH3:40]
Reactant: CCOP(OCC)OCC
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)CCCCCCCCCCCCCCCCCCCCCCBr
Product: CCOP(=O)(CCCCCCCCCCCCCCCCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)OCC
Temperature: 150 °C
Reaction time: 18 h
Yield: 101.7 %

Procedure:
A mixture of 0.98 g of 1-bromo-22-(nonafluorobutyl)docosane and 4.00 g of triethyl phosphite was heated at 150° C. After 18 hr, diethyl ethylphosphonate and other volatiles were distilled, b.p. 30-50° C. at 0.05 torr (7 Pa), leaving 1.09 g of 1-(diethylphosphono)-22-(nonafluorobutyl)docosane as an off-white solid, which was used without further purification.
Reaction SMILES: [BH4-].[Na+].[C:3]1([S:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>CO.C1COCC1.O.O.O.O.O.O.[Ni](Cl)Cl>[C:3]1([S:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=[N+]([O-])c1ccc(Sc2ccccc2)cc1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Nc1ccc(Sc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Nickel chloride hexahydrate (41 g, 172.5 mmol), then sodium borohydride (19.5 g, 0.516 mmol) were added to a solution of 4-nitrophenyl phenyl sulfide Compound 161a (20 g, 86.5 mmol) in a mixture of MeOH (200 mL) and THF (75 mL) at 0° C. under nitrogen over a period of 1 hr. The mixture was stirred for 30 mins at 0° C. and the reaction was quenched slowly with aqueous 10% NH4Cl, neutralized with ammonium hydroxide and partitioned between ethyl acetate and water. The organic layer was dried (Na2SO4), then filtered and the solvent evaporated in vacuo to yield 4-phenylsulfanyl-phenylamine Compound 161b (15.08 g, 87%), as a solid. MS (ES+) m/z 202.1 (M+H+). 1H NMR (400 MHz, CDCl3) δ 7.32-7.29 (2H, m), 7.22-7.18 (2H, m), 7.13-7.09 (3H, m), 6.68-6.66 (2H, m), 3.79 (2H, br s)
Reaction SMILES: [CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[CH2:22][NH2:23])[CH2:2][CH2:3][CH3:4].[CH3:24][N:25]1[C:29]([S:30](Cl)(=[O:32])=[O:31])=[CH:28][N:27]=[C:26]1[CH3:34].C(N(C(C)C)CC)(C)C>ClCCl>[CH2:1]([C:5]1[N:9]([C:10]2[N:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[C:13]([CH3:21])=[CH:12][N:11]=2)[N:8]=[CH:7][C:6]=1[CH2:22][NH:23][S:30]([C:29]1[N:25]([CH3:24])[C:26]([CH3:34])=[N:27][CH:28]=1)(=[O:32])=[O:31])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1c(CN)cnn1-c1ncc(C)c(-c2cccs2)n1
Reactant: Cc1ncc(S(=O)(=O)Cl)n1C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCc1c(CNS(=O)(=O)c2cnc(C)n2C)cnn1-c1ncc(C)c(-c2cccs2)n1

Procedure:
The title compound was prepared by mixing a sample of (5-butyl-1-(5-methyl-4-(thiophen-2-yl)pyrimidin-2-yl)-1H-pyrazol-4-yl)methanamine, (from Step 3 of Example 36), 1,2-dimethyl-1H-imidazole-5-sulfonyl chloride and diisopropylethylamine in dichloromethane. 1H NMR (400 MHz, CD3OD) δ 8.68 (s 1H), 7.94 (m, 1H), 7.78 (m, 1H), 7.56 (m, 1H), 7.37 (m, 1H), 7.29 (m, 1H), 4.09 (s 2H), 3.70 (s 3H), 3.18 (br t, 2H), 2.64 (s, 3H), 2.35 (s, 3H), 1.49 (m, 2H), 1.32 (m, 2H), 0.84 (m 3H). LCMS (ES+) m/z 486 (M+1).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B1OC(C)(C)C(C)(C)O1.Br[C:19]1[CH:24]=[CH:23][N:22]=[C:21]2[NH:25][CH:26]=[CH:27][C:20]=12.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21]2[NH:25][CH:26]=[CH:27][C:20]=12
Reactant: Brc1ccnc2[nH]ccc12
Reactant: CNc1ccccc1B1OC(C)(C)C(C)(C)O1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CNc1ccccc1-c1ccnc2[nH]ccc12
Temperature: 80 °C

Procedure:
A 1000 mL round bottom flask containing N-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (18.88 g, 81 mmol) was charged with 4-bromo-1H-pyrrolo[2,3-b]pyridine (11.40 g, 57.9 mmol), potassium phosphate (36.8 g, 174 mmol) and phenylallylchloro[1,3-bis(diisopropylphenyl)-2-imidazol-2-ylidene]palladium (II) (1.873 g, 2.89 mmol) under argon. To this was added a mixture of dioxane (400 mL) and water (100 mL) that had been degassed with argon for 30 minutes. The mixture was purged with nitrogen again, and heated at 80° C. overnight under nitrogen. The reaction mixture was cooled to ambient temperature and partitioned between ethyl acetate (750 mL) and 50% brine (1000 mL). The organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was dissolved in a minimum of methylene chloride, diluted with an equal volume of heptane and was purified on a Teledyne CombiFlash RF chromatography system on a silica gel Gold Rf cartridge (330 g) eluted with a 5-30% 3:1 ethyl acetate/ethanol in heptane to give the title compound. MS (ESI+) m/z 224 (M+1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([Si:8]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([Br:27])[CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:28]1[C:36]23[CH:37]=[CH:38][CH:39]=[CH:40][C:35]2=CO[C:32]3=[C:31]([C:41]2[CH:42]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=[CH:45][CH:46]=2)[CH:30]=[CH:29]1.[C:56]([O-:59])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.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>[Br:27][C:23]1[CH:22]=[C:21]([Si:8]([C:4]2[CH:3]=[C:2]([C:45]3[CH:44]=[CH:43][CH:42]=[C:41]([C:31]4[C:32]5[O:59][C:56]6[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=6[C:36]=5[CH:28]=[CH:29][CH:30]=4)[CH:46]=3)[CH:7]=[CH:6][CH:5]=2)([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:26]=[CH:25][CH:24]=1
Reactant: O=C([O-])[O-]
Reactant: Brc1cccc([Si](c2ccccc2)(c2ccccc2)c2cccc(Br)c2)c1
Reactant: CC1(C)OB(c2cccc(C3=C4OC=C5C=CC=CC54CC=C3)c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Product: Brc1cccc([Si](c2ccccc2)(c2ccccc2)c2cccc(-c3cccc(-c4cccc5c4oc4ccccc45)c3)c2)c1
Temperature: 25 °C
Yield: 60.1 %

Procedure:
A mixture solution of bis(3-bromophenyl)diphenylsilane (8.01 g, 16.21 mmol), 2-(3-(dibenzo[b,c]furan-4-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.00 g, 8.10 mmol), K2CO3 (2.240 g, 16.21 mmol), Pd(PPh3)4 (0.15 g, 0.162 mmol) in toluene (200 mL) and water (50 mL) was refluxed under nitrogen overnight. After cooling to room temperature, the organic phase was isolated and evaporated to dryness. The residue was purified by column chromatography on silica gel with hexane:DCM (9/1 to 3/1, v/v) as eluent to yield (3-bromophenyl)(3′-(dibenzo [b,d]furan-4-yl)-[1,1′-biphenyl]-3-yl)diphenylsilane (3.2 g, 60%) as a white solid.