Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:29]([CH3:34])([C:30]([NH:32][NH2:33])=[O:31])[C:28](=[O:35])[NH:27][C:4]=2[N:5]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=3)[C:10]([CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])=[N:9]2)[N:7]=1.[C:36](N1C=CN=C1)(=[O:38])[CH3:37]>C1COCC1>[C:36]([N:32]([C:30]([C:29]1([CH3:34])[C:3]2[C:2]([NH2:1])=[N:7][C:6]([N:8]3[C:16]4[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=4)[C:10]([CH2:18][CH2:19][C:20]([F:25])([F:26])[C:21]([F:23])([F:24])[F:22])=[N:9]3)=[N:5][C:4]=2[NH:27][C:28]1=[O:35])=[O:31])[NH2:33])(=[O:38])[CH3:37]
Reactant: CC(=O)n1ccnc1
Reactant: CC1(C(=O)NN)C(=O)Nc2nc(-n3nc(CCC(F)(F)C(F)(F)F)c4cc(Cl)ccc43)nc(N)c21
Solvent: C1CCOC1
Product: CC(=O)N(N)C(=O)C1(C)C(=O)Nc2nc(-n3nc(CCC(F)(F)C(F)(F)F)c4cc(Cl)ccc43)nc(N)c21

Procedure:
To a THF solution (3 mL) of the intermediate from Step A (100 mg, 0.193 mmol) was added 1-acetylimidazole (85 mg, 0.771 mmol). The resultant mixture was stirred at ambient temperature under a nitrogen atmosphere for 3 hours then purified by preparative TLC using 10% MeOH/1% NH4OH I DCM as eluent to give the indicated product. m/z=561.1 (M+H).
Reaction SMILES: C(ON=O)(C)(C)C.[C:8]([O:11][CH2:12][C:13]([CH2:15]Br)=[CH2:14])(=[O:10])[CH3:9].[N+:17]([C:20]1[CH:21]=[C:22]([CH:24]=[C:25]([N+:27]([O-:29])=[O:28])[CH:26]=1)N)([O-:19])=[O:18]>CC#N>[C:8]([O:11][CH2:12][C:13](=[CH2:14])[CH2:15][C:22]1[CH:21]=[C:20]([N+:17]([O-:19])=[O:18])[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=1)(=[O:10])[CH3:9]
Reactant: C=C(CBr)COC(C)=O
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: C=C(COC(C)=O)Cc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.9 %

Procedure:
To a solution of t-butylnitrite (0.47 ml, 4.0 mmol) and 2-acetoxymethyl-3-bromopropene (1.93 g, 10.0 mmol) in 1 ml CH3CN, 3,5-dinitroaniline (0.37 g, 2.0 mmol) was added, while maintaining the temperature between 18 and 24° C. The mixture was stirred for 1 h at room temperature. The volatile material in the solution was removed at reduced pressure. Flash chromatography (heptane/ethylacetate) gave 0.42 g 1-(2-acetoxymethyl-2-propenyl)-3,5-dinitrobenzene. 1H-NMR (CDCl3, 300 MHz) δ ppm: 8.94 (t, J=2.1 Hz, 1H), 8.42 (d, J=2.1 Hz, 2H), 5.33 (s, 1H), 5.05 (s, 1H), 4.52 (s, 2H), 3.64 (s, 2H), 2.08 (s, 3H). 13C-NMR (CDCl3, 75.43 MHz) δ ppm: 170.4, 148.5, 143.1, 140.7, 129.1, 117.5, 117.2, 65.9, 39.3, 20.7.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6].Br[CH2:15][CH2:16][O:17][CH3:18].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:13][O:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[O:1][CH2:15][CH2:16][O:17][CH3:18]
Reactant: COC(=O)c1ccc(OC)c(O)c1
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COCCOc1cc(C(=O)OC)ccc1OC
Temperature: 90 °C
Yield: 85.1 %

Procedure:
According to the procedure described in Example 6A Step 1, a mixture of methyl 3-hydroxy-4-methoxybenzoate (5.00 g, 27.4 mmol), 1-bromo-2-methoxyethane (4.96 g, 35.7 mmol), and K2CO3 (4.6 g, 32.9 mmol) in DMF (20 mL) was heated at 90° C. overnight, to afford methyl 4-methoxy-3-(2-methoxyethoxy)benzoate as a solid (5.6 g, 85%). 1H NMR (300 MHz, DMSO-d6) δ 7.60 (dd, 1H), 7.46 (d, 1H), 7.09 (d, 1H), 4.12 (m, 2H), 3.84 (s, 3H), 3.81 (s, 3H), 3.67 (m, 2H), 3.33 (s, 3H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:14][C:15]2[CH:19]=[C:18]([CH3:20])[NH:17][N:16]=2)[N:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=1>>[CH3:20][C:18]1[NH:17][N:16]=[C:15]([NH:14][C:4]2[N:3]=[C:2]([C:23]3[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=3)[C:11]3[C:6]([CH:5]=2)=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=3)[CH:19]=1
Reactant: OB(O)c1cccnc1
Reactant: COc1cccc2c(Cl)nc(Nc3cc(C)[nH]n3)cc12
Product: COc1cccc2c(-c3cccnc3)nc(Nc3cc(C)[nH]n3)cc12

Procedure:
Similar procedure as described in example 131 was used, starting from (1-chloro-5-methoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine and 3-pyridine-boronic acid to give (5-methyl-1H-pyrazol-3-yl)-(1-pyridin-3-yl-5-methoxy-isoquinolin-3-yl)-amine. LC-MS m/e 332(MH+).
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[C:3](O)([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]=1.C(N(S(F)(F)[F:40])CC)C.O>ClCCl>[F:1][C:2]([F:33])([F:32])[C:3]([F:40])([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]=1
Reactant: CCN(CC)S(F)(F)F
Reactant: OC(CCCc1cccc(Oc2ccccc2)c1)(c1ccc(OC(F)(F)F)cc1)C(F)(F)F
Solvent: ClCCl
Solvent: O
Product: FC(F)(F)Oc1ccc(C(F)(CCCc2cccc(Oc3ccccc3)c2)C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of 1,1,1-trifluoro-2-hydroxy-2-(4-trifluoromethoxyphenyl)-5-(3-phenoxyphenyl)pentane (0.18 g) in dichloromethane (6 cm3) was cooled to -78° C. and diethylaminosulphur trifluoride (0.1 g) was added. The mixture was allowed to warm to room temperature, stirred for a further 20 minutes and poured into water. The products were extracted into dichloromethane. The combined organic extracts were dried and the solvent evaporated under reduced pressure to leave an oil. The oil was purified by chromatography to give 1,1,1,2-tetrafluoro-2-(4-trifluoromethoxyphenyl)-5-(3-phenoxyphenyl)pentane.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][NH:9][C:10]2[N:11]=[C:12]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:13][C:14]=2[C:15]([NH2:17])=[O:16])[CH:5]=[CH:6][CH:7]=1.[C:25](OCC(Cl)=O)(=[O:27])[CH3:26].[OH-].[Na+].Cl>COCCOC.CO>[Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][N:9]2[C:10]3[N:11]=[C:12]([N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[S:13][C:14]=3[C:15](=[O:16])[N:17]=[C:26]2[CH2:25][OH:27])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)OCC(=O)Cl
Reactant: Cc1c(Cl)cccc1CNc1nc(N2CCOCC2)sc1C(N)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: COCCOC
Solvent: CO
Product: Cc1c(Cl)cccc1Cn1c(CO)nc(=O)c2sc(N3CCOCC3)nc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (1 g, 2.73 mmol) in 1,2-Dimethoxyethane (DME) (20 ml) at 0° C. was added acetoxyacetyl chloride (0.586 ml, 5.45 mmol). The mixture was stirred at room temperature for 2 h, then stirred at 50° C. overnight. The mixture was quenched with methanol and concentrated. To the resulting residue in Methanol (12 ml) was added 6N NaOH (0.9 mL, 5.45 mmol). The mixture was stirred at room temperature for 60 min, then acidified (˜pH 5) with 1N HCl. The solvent was removed and the residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. Reversed-phase HPLC purification provided 4-[(3-chloro-2-methylphenyl)methyl]-5-(hydroxymethyl)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (250 mg, 22%); LC/MS: MS (ES+) m/e 407 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.51 (m, 4H), 3.67 (m, 4H), 4.32 (d, J=5.6 Hz, 2H), 5.57 (s, 2H), 5.64 (t, J=5.6 Hz, 1H, OH), 6.51 (d, J=7.6 Hz, 1H), 7.14 (m, 1H), 7.37 (d, J=7.8 Hz, 1H).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([CH2:24][CH2:25][NH:26][C:27](=[O:41])[C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][N:37]=[C:36](Cl)[N:35]=4)=[CH:30][CH:29]=3)[CH:22]=2)[NH:17][CH:16]=1)#[N:14]>>[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([CH2:24][CH2:25][NH:26][C:27](=[O:41])[C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][N:37]=[C:36]([NH:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][N:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[N:35]=4)=[CH:30][CH:29]=3)[CH:22]=2)[NH:17][CH:16]=1)#[N:14]
Reactant: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(Cl)n4)cc3)cc12
Reactant: NCCCCCCN1CCCC1
Product: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(NCCCCCCN5CCCC5)n4)cc3)cc12

Procedure:
Using 6-pyrrolidin-1-ylhexylamine (reference example 93e) and N-[2-(3-Cyano-1H-indol-5-yl)-ethyl]-4-[2-chloro-pyrimidin-4-yl]-benzamide (reference example 1az) as substrates. MS (ion spray) m/z 536 (M+H)+.
Reaction SMILES: [C:1]1([C:7](=O)[CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-])=O)[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.C.[H][H]>C(O)(=O)C.[Pd]>[C:1]1([CH2:7][CH2:8][CH2:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[NH2:16])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(C=Cc1cccc([N+](=O)[O-])c1)c1ccccc1
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: Nc1cccc(CCCc2ccccc2)c1
Yield: 71.1 %

Procedure:
253 g of 1-phenyl-3-(3'-nitrophenyl)-prop-2-en-1-one are suspended in 2.5 liters of glacial acetic acid. 196 g of concentrated sulfuric acid and 10 g of 10% strength Pd on animal charcoal are added and the mixture is hydrogenated under 1.1 bar hydrogen pressure at 65°-70° C., until no further hydrogen is absorbed. When the mixture has cooled, some of the acetic acid is distilled off, the residue is rendered alkaline with sodium hydroxide solution and extracted by shaking with ether, the organic phase is dried over sodium sulfate and filtered, the solvent is stripped off and the residue is distilled. 150 g of 3-(3-phenylpropyl)-aniline of boiling point 148° C./0.2 mbar are obtained.
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[CH2:5].[F-].[Cs+].[F:20][C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[OH:38])=[O:31])[CH:24]=[CH:25][C:26]=1[F:27]>CS(C)=O>[F:20][C:21]1[CH:22]=[C:23]([CH:28]([CH2:3][C:4]([C:6]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:7]=2)=[O:5])[CH2:29][C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[OH:38])=[O:31])[CH:24]=[CH:25][C:26]=1[F:27]
Reactant: C=C(O[Si](C)(C)C)c1ccc2ccccc2c1
Reactant: O=C(C=Cc1ccc(F)c(F)c1)c1ccccc1O
Agent: [Cs+]
Agent: [F-]
Solvent: CS(C)=O
Product: O=C(CC(CC(=O)c1ccccc1O)c1ccc(F)c(F)c1)c1ccc2ccccc2c1
Temperature: 70 °C

Procedure:
1-Trimethylsilyloxy-1-(naphthalen-2-yl)ethylene (7.0 mol; prepared according to J. Chem. Soc., Perkin Trans. I 1989, 1585) and CsF (0.27 g, 1.76 mmol) were added to a suspension of 3-(3,4-difluorophenyl)-1-(2-hydroxyphenyl)-2-propen-1-one on Wang resin (2.0 g, 1.76 mmol) in dimethyl sulfoxide (30 mL). The reaction mixture was heated to 70° C. for 3 h and the reaction was quenched with 10% AcOR/CH2Cl2. The resin was filtered, washed with DMF (×2) and alternating MeOH and CH2Cl2 (×5), and dried under high vacuum overnight to give 3-(3,4-difluorophenyl)-1-(2-hydroxyphenyl)-5-(naphthalen-2-yl)-1,5-pentanedione on Wang resin.
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:39])[NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[O:32])[CH:25]=3)=[CH:15][CH:14]=2)[N:7]([C:40]2[CH:45]=[CH:44][C:43]([O:46][Si](C(C)C)(C(C)C)C(C)C)=[C:42]([Cl:57])[CH:41]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CO>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:39])[NH:12][C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[O:32])[CH:25]=3)=[CH:15][CH:14]=2)[N:7]([C:40]2[CH:45]=[CH:44][C:43]([OH:46])=[C:42]([Cl:57])[CH:41]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)[Si](Oc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(Oc3ccnc(NC(=O)N4CCOCC4)c3)c3ccccc23)cc1Cl)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccnc(NC(=O)N4CCOCC4)c3)c3ccccc23)n(-c2ccc(O)c(Cl)c2)n1
Reaction time: 16 h

Procedure:
To a solution of N-(4-(4-(3-(3-tert-butyl-1-(3-chloro-4-(triisopropylsilyloxy)phenyl)-1H-pyrazol-5-yl)ureido)naphthalen-1-yloxy)pyridin-2-yl)morpholine-4-carboxamide (70 mg, 0.078 mmol) in dry THF (2.0 mL) was added TBAF (1.0 M in THF, 116 μL, 0.116 mmol) and the reaction mixture kept at RT for 16 hr. The reaction mixture was diluted with MeOH (1.0 mL) and after 5 min was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 4 g, EtOAc in isohexane, 0-100%, gradient elution) to afford the title compound, Example 12, as a pink solid (20 mg, 39%); Rt 3.97 min (Method 1 basic); m/z 655 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) δ: 1.27 (9H, s), 3.36 (4H, m), 3.52 (4H, m), 6.37 (1H, s), 6.61 (1H, dd), 7.12 (1H, d), 7.31 (1H, d), 7.35 (1H, dd), 7.37 (1H, d), 7.54 (1H, d), 7.57 (1H, m), 7.64 (1H, m), 7.84 (1H, d), 7.91 (1H, br s), 8.06 (1H, d), 8.12 (1H, d), 8.74 (1H, s), 9.09 (1H, s), 9.26 (1H, s), 10.62 (1H, br s).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][C:10]1[C:15]([NH2:16])=[CH:14][C:13]([C:17]2([CH3:20])[CH2:19][CH2:18]2)=[CH:12][C:11]=1[NH2:21].[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl>[NH2:21][C:11]1[C:10]([O:9][CH3:8])=[C:15]([NH:16][S:23]([CH3:22])(=[O:25])=[O:24])[CH:14]=[C:13]([C:17]2([CH3:20])[CH2:19][CH2:18]2)[CH:12]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1c(N)cc(C2(C)CC2)cc1N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1c(N)cc(C2(C)CC2)cc1NS(C)(=O)=O
Temperature: 25 °C
Yield: 50.4 %

Procedure:
Triethylamine (521 mL, 3.74 mmol) was added to a solution of 2-methoxy-5-(1-methyl-cyclopropyl)-benzene-1,3-diamine (718 mg, 3.74 mmol) in methylene chloride at −10° C. Methanesulfonyl chloride (290 μL, 3.74 mmol) was then added dropwise over a 10 min period and the resultant solution was allowed to slowly warm to rt over 2 h. The mixture was quenched with saturated aqueous NaHCO3 and the aqueous layer was extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (1% ammonium hydroxide/35% ethyl acetate in hexanes to 1% ammonium hydroxide/50% ethyl acetate in hexanes) provided a red solid which was triturated with a diethyl ether/hexanes (1:1) to yield Compound 1 (510 mg, 51%) as a pale brown solid: mp 144–146° C. ESI MS (m/z 271, M+H).
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.[CH3:22][CH:23](C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Zn](CC)CC>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:22]([C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2)[CH3:23]
Reactant: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Agent: [Pd]
Agent: CC[Zn]CC
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1CCOC1
Product: CCc1nc2cc(C(=O)OC)ccc2nc1-c1ccccc1
Temperature: 80 °C
Yield: 570.1 %

Procedure:
A suspension of methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (100 mg, 0.29 mmol, 1.00 equiv), X-phos (14 mg, 0.03 mmol, 0.10 equiv), Pd2(dba)3 (27 mg, 0.03 mmol, 0.10 equiv) in THF (10 mL), and Et2Zn in THF (5.8 mL, 20.00 equiv, 1M was allowed to react, with stifling, overnight while the temperature was maintained at 80° C. in an oil bath. The reaction was quenched by the addition of 2 mL of water. The resulting mixture was concentrated under vacuum and purified by prep-TLC (petroleum ether:ethyl acetate (4:1)) yielding 50 mg (35%) of methyl 3-ethyl-2-phenylquinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: CC(=C)C([C:18]1(O)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)C[Si](CCCC)(CCCC)CCCC.C[C:27]([C:44]1(O)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1)([CH2:30][Si:31]([CH2:40][CH2:41][CH2:42][CH3:43])([CH2:36][CH2:37]CC)CCCC)C=C.CC(C)=CCCC(=C)C(C1(O)CCCCC1)C[Si](C)(C)C.C(C(C1(O)CCCCC1)(C[Si](C)(C)C)CCC=C(C)C)=C>O>[C:18]1([C:42]2[CH2:43][Si:31]3([CH2:36][CH:37]=[C:27]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)[CH2:30]3)[CH2:40][CH:41]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: C=CC(C)(C[Si](CCCC)(CCCC)CCCC)C1(O)CCCCC1
Reactant: C=C(C)C(C[Si](CCCC)(CCCC)CCCC)C1(O)CCCCC1
Agent: C=C(CCC=C(C)C)C(C[Si](C)(C)C)C1(O)CCCCC1
Agent: C=CC(CCC=C(C)C)(C[Si](C)(C)C)C1(O)CCCCC1
Solvent: O
Product: C1=C(c2ccccc2)C[Si]2(C1)CC=C(c1ccccc1)C2

Procedure:
1-(2-Methyl-I-tri(n-butyl)silylmethyl-2-propenyl)cyclohexanol and 1-(1-Methyl-1-(tri-n-butyl)silylmethyl-2-propenyl)cyclohexanol (92:8, 94% total yield). Major isomer: 1H NMR δ 4.85 (m, 1 H), 4.77 (d, J=1.9 Hz, 1 H), 2.12 (dd, J=8.5, 6.1 Hz, 1 H), 1.76 (d, J=0.4 Hz, 3 H), 1.68-1.10 (m, 22 H), 0.87 (t, J=7.0 Hz, 9 H), 0.76-0.70 (m, 2 H), 0.52-4.44 (m, 6 H); 13C NMR δ 147.2, 114.1, 73.2, 52.3, 35.6, 35.5, 26.9, 26.2, 25.9, 22.3, 22.2, 13.8, 12.4, 9.8; IR (neat) 3491 (br), 3068, 2954, 2924, 2870, 2856, 1637, 1456, 1375, 1196, 1082, 964, 887 cm-1 ; EIMS m/z (relative intensity) 309 ([M--C4H9 ]+ 0.5), 297 (4.3), 268 (7.8), 199 (100), 143 (67), 99 (19); HRMS calcd for C23H46OSi and C2213CH46OSi: 366.3318, 367.3347, found (EI Peak Match): 366.3301, 367.3338. Anal. Calcd: C, 75.33; H, 12.64. Found: C, 75.60; H, 12.77. Minor Isomer (difficult to isolate): 1H NMR δ 5.92 (dd, J=17.6, 10.8 Hz, 1 H), 5.11 (dd, J=10.8, 1.2 Hz, 1 H), 5.01 (dd, J=17.6, 1.2 Hz, 1 H), 1.70-1.10 (m, 22 H), 1.07 (s, 3 H), 0.88 (t, J=7.0 Hz, 9 H), 0.95-0.75 (m, 2 H), 0.53-0.45 (m, 6 H). 1-(2-(4-Methyl-3-pentenyl)-1-trimethylsilylmethyl-2-propenyl)cyclohexanol and 1-(1-Ethenyl-5-methyl-1-trimethylsilylmethyl-4-hexenyl)cyclohexanol (94:6). Major isomer: 1H NMR δ 5.17- 5.09 (m, 1 H), 4.89 (s, 1 H), 4.86 (s, 1 H), 2.20-2.00 (m, 5 H), 1.67 (s, 3 H), 1.60 (s, 3 H), 1.68-1.05 (m, 10 H), 0.84-0.69 (m, 2 H), 0.03 (s, 9 H); 13C NMR δ 151.1, 131.5, 124.4, 111.4, 73.2, 53.0, 35.6, 35.5, 25.9, 25.8, 25.7, 22.3, 22.1, 17.6, 14.9, -0.9; IR (neat) 3485 (br), 3080, 2931, 2858, 1633, 1448, 1375, 1246, 972, 891, 860, 837 cm-1 ; EIMS m/z (relative intensity) 290 ([M--H2O]+, 0.3), 275 (0.2), 210 (7), 171 (28), 141 (87), 99 (16), 73 (100); HRMS calcd for C19H36OSi and C1813CH36OSi: 308.2535, 309.2563, found (HREI Peak Match): 308.2530, 309.2559. Anal. Calcd: C, 73.96; H, 11.76. Found: C, 74.15; H, 11.80. Minor isomer: 1H NMR δ 5.81 (dd, J=17.6, 11.0 Hz, 1 H), 5.15-4.95 (m, 3 H), 2.10-0.95 (m, 14 H), 1.65 (s, 3 H), 1.59 (s, 3 H), 0.91 (d, J=15.0 Hz, 1 H), 0.75 (d, J=15.0 Hz, 1 H), 0.04 (s, 9 H); 13C NMR δ 145.5, 131.0, 125.3, 114.1, 75.8, 50.6, 33.3, 31.6, 31.5, 25.7, 24.0, 22.0, 21.8, 19.8, 17.8, 1.6; IR (neat) 3566 (br), 3080, 2933, 2858, 1631, 1450, 1375, 1259, 1246, 1155, 958, 912, 860, 845 cm-1.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>ClCCl>[CH3:13][S:14]([N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: C1CCNC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCCC1
Temperature: 25 °C

Procedure:
To a solution of pyrrolidine (8.25 g, 116 mmol) in dichloromethane (120 mL) were added triethylamine (19.0 mL, 139 mmol) followed by addition of methanesulfonyl chloride (9.0 mL, 116 mmol) at 0° C. The reaction was allowed to stir while warming up to rt. overnight, which was transferred to a separatory funnel and washed twice with 1.0N HCl and brine once. Organic phase was dried over magnesium sulfate, filtered and solvent was removed to leave a pure title product as a white solid. Step B: 1-(Pyrrolidin-1-ylsulfonyl)propan-2-one
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[CH:12]([NH2:15])([CH3:14])[CH3:13]>>[CH3:13][CH:12]([NH:15][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[CH3:14]
Reactant: CC(C)N
Reactant: Oc1ccc(OCCBr)cc1
Product: CC(C)NCCOc1ccc(O)cc1
Yield: 59 %

Procedure:
4-(2-Bromoethoxy)phenol (41 g) was added to 300 ml of isopropylamine and the solution was heated for 12 hours at 100° under nitrogen at 250 psi. Excess isopropylamine was removed in vacuo and 300 ml of water added to dissolve the residue. The solution was basified with solid potassium carbonate and the oil extracted with ether. The ether extract was dried over anhydrous potassium carbonate. After the solvent was removed in vacuo and the residue was crystallized from acetone-hexane to yield 21.8 g (59%) of 4-[2-(1-methylethyl)aminoethoxy]phenol, mp 78°-80°.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([CH:15]([OH:20])[CH2:16][CH2:17][CH2:18][CH3:19])[CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.O[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:26][CH:25]=1.P(CCCC)(CCCC)CCCC>C1COCC1>[F:22][C:2]([F:21])([F:1])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]([CH:15]([O:20][C:24]3[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:26][CH:25]=3)[CH2:16][CH2:17][CH2:18][CH3:19])[CH:12]=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: CCCCC(O)c1cccc(-c2ccc(C(F)(F)F)cc2)n1
Reactant: CCOC(=O)CCc1ccc(O)cc1
Agent: CCCCP(CCCC)CCCC
Solvent: C1CCOC1
Product: CCCCC(Oc1ccc(CCC(=O)OCC)cc1)c1cccc(-c2ccc(C(F)(F)F)cc2)n1
Temperature: 0 °C
Yield: 37.3 %

Procedure:
To a stirred solution of the 1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}-1-pentanol (50 mg, 0.16 mmol) and ethyl 3-(4-hydroxyphenyl)propanoate (31 mg, 0.16 mmol) in anhydrous THF (3.2 mL) under nitrogen at 0° C. (ice/water bath) was added ADDM (83 mg, 0.32 mmol). After a few minutes, nBu3P (81 μL, 0.32 mmol) was added (drop-wise) and the solution was stirred at 0° C. warming to rt overnight. After 17.5 hours the solvent was concentrated under vacuum and the solid residue dissolved in DCM (5 mL) and washed with water (5 mL) using a hydrophobic frit. The aqueous layer was re-extracted with DCM (5 mL) and the combined organic layers concentrated under vacuum. The resulting solid residue was then purified by SPE (silica, 5 g cartridge) eluting with cyclohexane:EtOAc (gradient 100:1 to 1:1) to afford the title compound (29 mg).
Reaction SMILES: [CH2:1]=[C:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(OCC)(=O)C>CN(C)C=O>[CH2:1]=[C:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O:5][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:4]
Reactant: C=C(Cc1ccccc1)C(=O)O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=C(Cc1ccccc1)C(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 60.1 %

Procedure:
The title acid of Step 9 (5.2 g, 30 mmol) was dissolved in dimethylformamide (25 mL) and cooled to 0° C. To this solution potassium carbonate (5.7 g, 41.48 mmol) was added followed by benzyl bromide (5.7 g, 29.7 mmol). The mixture was stirred at room temperature overnight. The mixture was filtered and the filtrate was diluted with ethyl acetate, washed with 3 times of water, brine. The solution was dried (Na2SO4) and evaporated. The residue was purified by flash chromotography on silica gel, eluting with 90:10 heptane:ethyl acetate to give the pure title compound as colorless oil (4.5 g, 60% yield). 1H NMR: 300 MHz spectrum consistent with proposed structure. Anal: calcd. for C17H16O2 : C, 80.93; H, 6.39. Found: C, 80.69; H, 6.47.