Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:25](Cl)(=[O:27])[CH3:26].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:25](=[O:27])[CH3:26])=[CH:21][CH:22]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)OC(=O)NCCc1ccc(Oc2ccc(N)cc2)cc1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ccc(Oc2ccc(CCNC(=O)OC(C)(C)C)cc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 88.5 %

Procedure:
Add a solution of {2-[4-(4-Amino-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.2 g, 3.66 mmol) in dichloromethane (25 mL) dropwise to a solution of acetyl chloride (0.35 g, 4.50 mmol) in dichloromethane (125 mL) at room temperature. Upon complete addition of the amine, add triethylamine (0.74 g, 7.32 mmol) and a crystal of DMAP to the reaction and stirred at room temperature for 18 hours. Add an additional 65 uL of acetyl chloride to the reaction and stir an additional 2 hours. Pour the reaction into saturated aqueous sodium bicarbonate then extract with dichloromethane (3×100 mL). Dry the dichloromethane extracts over sodium chloride/magnesium sulfate, filter, then concentrate on a rotary evaporator to yield 1.3 g of the crude product. The crude product is purified by flash column chromatography on silica gel eluting with ethyl acetate and hexanes to yield {2-[4-(4-acetylamino-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.2 g): 1H NMR (CDCl3, 300.00 MHz): 8.00 (s, 1H), 7.49 (d, 2H, J=8.8 Hz), 7.13 (d, 2H, J=8.4 Hz), 6.98-6.89 (m, 4H), 4.69 (s, 1H), 3.37 (d, 2H, J=6.2 Hz), 2.77 (t, 2H, J=7.0 Hz), 2.18 (s, 3H), 1.46 (s, 9H).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([C:12]#[C:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].O.[OH-].[Li+]>CO>[CH3:15][C:14]([CH3:17])([CH3:16])[C:13]#[C:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([OH:6])=[O:5])=[C:2]([F:1])[CH:11]=1
Reactant: COC(=O)c1ccc(C#CC(C)(C)C)cc1F
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)C#Cc1ccc(C(=O)O)c(F)c1
Temperature: 25 °C

Procedure:
Methyl 2-fluoro-4-(3,3-dimethylbut-1-ynyl)benzoate (8.2 g, 0.035 mol) was suspended in a 3:1 mixture of H2O and methanol to which was added lithium hydroxide (2.5 g, 0.10 mol) all at once and the mixture was agitated over-night at ambient temperature. The mixture was then concentrated to ¾ the volume and acidified with 1N HCl until the pH read just acidic. The white precipitate was filtered, washed with water and vacuum dried at 80° C. for several hours. m/z=218.9 (M−1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3=[CH:12][S:13][CH:14]=[C:9]3[C:8](=[S:15])[NH:7][C:6]=2[CH:16]=1.[OH-].[K+].S([O-])(O[CH3:23])(=O)=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3=[CH:12][S:13][CH:14]=[C:9]3[C:8]([S:15][CH3:23])=[N:7][C:6]=2[CH:16]=1
Reactant: COS(=O)(=O)[O-]
Reactant: Fc1ccc2c(c1)NC(=S)c1cscc1N2
Agent: [K+]
Agent: [OH-]
Product: CSC1=Nc2cc(F)ccc2Nc2cscc21

Procedure:
In a similar manner 7-fluoro-4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-thione is reacted with potassium hydroxide and methyl sulfate to give 7-fluoro-10-(Methylthio)-4H-thieno[3,4-b][1,5]benzodiazepine.
Reaction SMILES: Cl.[CH3:2][N:3]1[C@@H:13]2[CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]4[O:23][CH:7]5[C:8]([CH:10]=[CH:11][C@:12]2([OH:24])[C@:6]5([C:16]=34)[CH2:5][CH2:4]1)=[O:9].CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5C(C=C[C@@H]2[C@]5(C=34)CC1)=O>>[CH3:2][N:3]1[C@@H:13]2[CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]4[O:23][C@H:7]5[C:8]([CH2:10][CH2:11][C@:12]2([OH:24])[C@:6]5([C:16]=34)[CH2:5][CH2:4]1)=[O:9]
Reactant: COc1ccc2c3c1OC1C(=O)C=C[C@@]4(O)[C@@H](C2)N(C)CC[C@]314
Agent: COc1ccc2c3c1O[C@H]1C(=O)C=C[C@H]4[C@@H](C2)N(C)CC[C@]314
Agent: Cl
Product: COc1ccc2c3c1O[C@H]1C(=O)CC[C@@]4(O)[C@@H](C2)N(C)CC[C@]314

Procedure:
A blank 0.1 M HCl, 0.25 mg/mL standards of 14-hydroxycodeinone and codeinone, 0.58 μg/mL and 0.58 μg/mL of an oxycodol in 0.1M HCL standard were prepared and then analysed using the above method. ˜1 mg/mL samples of the post hydrogenation liquors and isolated oxycodone alkaloid were also prepared in 0.1M HCl.
Reaction SMILES: N[C@@H]1CCC[C@H]1O.[NH2:8][C@@H:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]1[OH:18].C1C2C(=CC=CC=2)[C@H](N)[C@@H]1O.C1C2C(=CC=CC=2)[C@@H](N)[C@H]1O.[C:41](N)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>>[C:41]([NH:8][C@@H:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]1[OH:18])(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: NC(=O)c1ccccc1
Reactant: N[C@@H]1c2ccccc2C[C@H]1O
Agent: N[C@@H]1CCC[C@H]1O
Agent: N[C@@H]1c2ccccc2C[C@@H]1O
Agent: N[C@H]1c2ccccc2C[C@H]1O
Product: O=C(N[C@@H]1c2ccccc2C[C@H]1O)c1ccccc1

Procedure:
In one embodiment the trans-1-amino-2-hydroxycyclopentane may be trans-1-amino-2-indanol. If the trans-1-amino-2-hydroxycyclopentane is trans-(1S,2S)-amino-2-indanol, it is converted to cis-(1S, 2R)-1-amino-2-indanol; if the trans-1-amino-2-hydroxycyclopentane is trans-(1R,2R)-1-amino-2-indanol, it is converted to cis-(1R,2S)-l-amino-2-indanol. When the amino alkanol is partially resolved trans-1-amino-2-indanol and the amide is a benzamide, an additional step of recrystallizing the benzamide produces substantially optically pure trans-1-benzamido-2-indanol.
Reaction SMILES: [CH2:1]([C:5]1[O:6][C:7]2[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=2[C:9]=1/[CH:10]=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]>CCOC(C)=O.[Pd]>[CH2:1]([C:5]1[O:6][C:7]2[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=2[C:9]=1[CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1oc2ccccc2c1/C=C\c1ccc(OC)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCc1oc2ccccc2c1CCc1ccc(OC)cc1

Procedure:
At ambient temperature, a solution containing cis-2-butyl-3-[2-(4-methoxy-phenyl)-vinyl]-benzofuran (0.400 g, 1.31 mmol) in EtOAc (5 mL) and 10% palladium on carbon (200 mg) was stirred under H2 (atmospheric conditions). The reaction was fitered and the filtrate concentrated to the title compound as a clear oil. 1H NMR (DMSO-d6) δ0.83 (t, 3 H), 1.20 (sextet, 2 H), 1.37 (quintet, 2 H), 2.49-2.52 (m, 2 H, with DMSO), 2.78-2.85 (m, 4 H), 3.68 (s, 3 H), 6.78 (d, 2 H), 7.03 (d, 2 H), 7.17-7.21 (m, 2 H), 7.41-7.43 (m, 1 H), 7.54-7.56 (m, 1 H). IR (KBr) 2950, 1610, 1510, 1450 and 1250 cm−1. mass spectrum (EI) m/z 308 (M +). Anal. Calcd. for C2,H24O2: C, 81.78; H, 7.84; N, 0.00. Found: C, 81.55; H, 7.57; N, 0.10.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH:13]1[C:21]3[C:16](=[CH:17][C:18]([F:22])=[CH:19][CH:20]=3)[CH2:15][CH2:14]1)[CH:6]=[CH:5]2.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=1>>[F:22][C:18]1[CH:17]=[C:16]2[C:21](=[CH:20][CH:19]=1)[CH:13]([NH:12][C:7]1[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=4)[CH:3]=3)[N:8]=1)[CH2:14][CH2:15]2
Reactant: Cc1cccc(N)n1
Reactant: Fc1ccc2c(c1)CCC2Nc1ccc2cc(Br)ccc2n1
Product: Cc1cccc(Nc2ccc3nc(NC4CCc5cc(F)ccc54)ccc3c2)n1

Procedure:
The title compound, yellow foam, MS: m/e=385.3 (M+H+), was prepared in accordance with the general method of example 66 from rac-(6-bromo-quinolin-2-yl)-(5-fluoro-indan-1-yl)-amine (see example 102, step A) and commercially available 2-amino-6-methyl-pyridine.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8](=[O:11])[NH:9][NH:10][C:4]=2[CH:3]=1.Cl[C:13]([O:15][CH2:16][CH3:17])=[O:14]>N1C=CC=CC=1.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8](=[O:11])[NH:9][N:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:4]=2[CH:3]=1
Reactant: O=c1[nH][nH]c2cc(Cl)ncc12
Reactant: CCOC(=O)Cl
Solvent: O
Solvent: c1ccncc1
Product: CCOC(=O)n1[nH]c(=O)c2cnc(Cl)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 6-chloro-1H-pyrazolo[4,3-c]pyridin-3(2H)-one (2.64 g, 15.57 mmol) in pyridine (10 mL) and water (14 mL) was added ethyl chloroformate (3.38 g, 31.1 mmol) drop-wise at 0° C. The reaction was removed from the ice bath and was stirred at room temperature overnight. The reaction mixture was filtered and the solid rinsed with water to afford ethyl 6-chloro-3-oxo-2,3-dihydro-1H-pyrazolo[4,3-c]pyridine-1-carboxylate, which was carried onto the next step without further purification. MS ESI calc'd. for C9H8ClN3O3 [M+1]+242. found 242.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][CH2:9][O:10][CH3:11])[C:6](=[S:12])[NH:5][C:4](=[O:13])[CH:3]=1.[N:14]([O-])=[O:15].[Na+].O>C(O)(=O)C>[NH2:1][C:2]1[N:7]([CH2:8][CH2:9][O:10][CH3:11])[C:6](=[S:12])[NH:5][C:4](=[O:13])[C:3]=1[N:14]=[O:15]
Reactant: O=N[O-]
Reactant: COCCn1c(N)cc(=O)[nH]c1=S
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: COCCn1c(N)c(N=O)c(=O)[nH]c1=S
Temperature: 75 °C
Yield: 36.5 %

Procedure:
6-Amino-1-(2-methoxy-ethyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (1.0 g, 5.0 mmol) was suspended in 10% acetic acid (20 mL). Sodium nitrite (0.38 g, 5.5 mmol) was added and the resulting mixture was heated at 75° C. for 1 h. The reaction mixture became first pink and then purple. Water (20 mL) was added and the reaction mixture was put in the fridge overnight. The purple solid was collected by filtration and washed with water to give the title compound (0.42 g, 37%). A second crop of product (0.22 g, 19%) was obtained by reducing the volume of the purple filtrate. The crude product was used in the following step without further purification.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH2:16])=[O:8])[N:6]=1.[N:24]1[CH:25]=[C:26]([C:33](O)=[O:34])[N:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=12>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH:16][C:33]([C:26]2[N:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]3=[N:24][CH:25]=2)=[O:34])=[O:8])[N:6]=1
Reactant: O=C(O)c1cnc2ccccn12
Reactant: NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1nc(N)sc1-c1cccc(F)c1
Product: Nc1nc(C(=O)N2C[C@@H]3C[C@@H]3[C@H]2CNC(=O)c2cnc3ccccn23)c(-c2cccc(F)c2)s1

Procedure:
prepared by reaction of [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone with Imidazo[1,2-a]pyridine-3-carboxylic acid. LC-MS (basic): tR=0.74 min; [M+H]+=477.3.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[Mg].II.[N:16]1([CH:21]([CH3:26])[C:22](OC)=[O:23])[CH:20]=[N:19][CH:18]=[N:17]1>O1CCCC1>[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:22]([C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:11])[F:12])=[CH:9][CH:8]=2)([OH:23])[CH:21]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)[CH3:26])=[CH:6][CH:5]=1
Reactant: COC(=O)C(C)n1cncn1
Reactant: FC(F)(F)Oc1ccc(Br)cc1
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(n1cncn1)C(O)(c1ccc(OC(F)(F)F)cc1)c1ccc(OC(F)(F)F)cc1
Temperature: 40 °C
Reaction time: 2 h
Yield: 11.6 %

Procedure:
A solution of 4-trifluoromethoxybromobenzene (9.3 g.) in dry tetrahydrofuran (40 cm3) was added dropwise to a stirred mixture of magnesium turnings (0.93 g.), dry tetrahydrofuran (15 cm3) and a crystal of iodine under a nitrogen atmosphere and at the ambient temperature. The reaction was observed to have commenced after 4 cm3 of the solution had been added. After the addition was complete the mixture was stirred for a further 2 hours. A solution of methyl 2-(1,2,4-1H-triazol-1-yl)propionate (3.0 g.) in dry tetrahydrofuran (5.0 cm3) was added dropwise to the mixture and after stirring for a further two hours at the ambient temperature the mixture was warmed to 40° C. for 3 hours. The mixture was then quenched with water, acidified with dilute hydrochloric acid and extracted with diethyl ether. The ethereal extract was washed with water (three times) and dried over anhydrous magnesium sulphate. The residual oil remaining after removal of the solvent by evaporation under reduced pressure was subjected to purification by hplc using a silica gel column eluted with a mixture of dichloromethane (3 parts by volume) and ethyl acetate (2 parts by volume) to give 1,1-bis(4-trifluoromethoxy- phenyl)-2-(1,2,4-1H-triazol-1-yl)propanol (1.0 g.) as a solid residue.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]([NH:17][C:18]([C:20]1([Br:27])[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][NH:21]1)=[O:19])([CH3:16])[CH3:15].[Cl:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=1)[CH2:32]Br>C1COCC1>[CH3:16][C:14]([NH:17][C:18]([C:20]1([Br:27])[C:25]([CH2:26][CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[C:29]([Cl:28])[CH:30]=2)=[CH:24][CH:23]=[CH:22][NH:21]1)=[O:19])([CH3:13])[CH3:15]
Reactant: Clc1cccc(CBr)c1
Reactant: CC1=CC=CNC1(Br)C(=O)NC(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(C)(C)NC(=O)C1(Br)NC=CC=C1CCc1cccc(Cl)c1
Reaction time: 0.5 h
Yield: 68.2 %

Procedure:
Cool diisopropylamine dissolved in THF (60 mL) to 0-5° C. Add n-butyl lithium(39 mL, 97.99 mmol.) and stir the reaction at that temperature for 30 min. Canulate this reaction mixture to a cooled solution of N-(1,1-dimethylethyl)-2-bromo-3-methyl pyridine carboxamide (9.91 g, 97.99 mmol) in dry THF (250 mL) (-70° C.). Stir for 0.5 h then add 3-chlorobenzyl bromide(11.4 g, 55.31 mmol) dissolved in 50 mL of THF. Stir the reaction mixture for 0.5 h. Quench the reaction with water and extract the products twice with EtOAc. Dry the organic phase over Na2SO4, filter and chromatograph on silica gel column eluting with 3% MeOH solution in CH2Cl2 to give the title compound (15 g, Yield 60%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH2:34]([S:37](Cl)(=[O:39])=[O:38])[CH2:35][CH3:36]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@@H:18]4[CH2:23][CH2:22][CH2:21][N:20]([S:37]([CH2:34][CH2:35][CH3:36])(=[O:39])=[O:38])[CH2:19]4)[C:14]([F:24])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Fc1cnc(-c2c[nH]c3ncc(Cl)cc23)nc1NC1CCCNC1
Reactant: CCCS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCCS(=O)(=O)N1CCC[C@@H](Nc2nc(-c3c[nH]c4ncc(Cl)cc34)ncc2F)C1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of 2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-N-(piperidin-3-yl)pyrimidin-4-amine, 5c, (0.40 g, 1.15 mmol) in 10:1 mixture of CH2Cl2/DMF (8 mL) was added iPr2NEt (0.60 mL, 3.46 mmol) followed by 1-propanesulfonyl chloride (0.13 mL, 1.15 mmol). The reaction mixture was stirred at room temperature for 5 hours. The resulting residue was purified by preparatory HPLC (0.1% TFA-H2O/acetonitrile) to afford the desired product, 316.
Reaction SMILES: [CH2:1]([OH:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH3:9][C:10]1[CH:11]=[C:12](I)[CH:13]=[C:14]([CH3:16])[CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCCCCCCCCCCC>[Cu]I.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:12]1[CH:13]=[C:14]([CH3:16])[CH:15]=[C:10]([CH3:9])[CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: Cc1cc(C)cc(I)c1
Reactant: CCCCCCCO
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCCCCCCCCCCC
Solvent: Cc1ccccc1
Product: CCCCCCCOc1cc(C)cc(C)c1
Temperature: 110 °C

Procedure:
A screw cap test tube was charged with n-heptanol (283 μL, 2.00 mmol), 3,5-dimethyliodobenzene (144 μL, 1.00 mmol), CuI (19.0 mg, 0.100 mmol), ligand (0.200 mmol), Cs2CO3 (977 mg, 3.00 mmol) and toluene (1 mL). The test tube was sealed with a screw cap. The reaction mixture was stirred magnetically and heated at 110° C. for 39 hours. The reaction mixture was allowed to reach room temperature. Dodecane (227 μL, 1.00 mmol; internal standard) was added and a GC sample was filtered through Celite and eluted with CH2Cl2. The yield of the desired product was determined using GC analysis; the results are tabulated below.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([CH2:12][OH:13])[CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1>C(Cl)Cl.O=[Mn]=O>[S:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=2)[CH:12]=[O:13])[N:3]=[CH:2]1
Reactant: OCc1cccc(-c2cscn2)c1
Agent: O=[Mn]=O
Solvent: ClCCl
Product: O=Cc1cccc(-c2cscn2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of (3-(thiazol-4-yl)phenyl)methanol (333 mg; 1.74 mmol) in anh. DCM (17 ml) was treated with MnO2 (2.276 g; 26.18 mmol), and the resulting mixture was stirred at rt, under nitrogen, for 1 h 45. The resulting reaction mixture was then filtered over celite, and the separated solids were washed with DCM. The filtrate was concentrated to dryness under reduced pressure giving 3-(thiazol-4-yl)benzaldehyde as a pale yellow solid. LC-MS (conditions A): tR=0.62 min.; [M+H]+: 190.13 g/mol.
Reaction SMILES: C([Mg]Br)C.[CH3:5][Si:6]([CH3:17])([CH3:16])[NH:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[CH2:13])=[CH:10][CH:9]=1.[CH3:18][Si:19](Cl)([CH3:21])[CH3:20]>C1COCC1>[CH3:17][Si:6]([CH3:5])([CH3:16])[N:7]([C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[CH2:13])=[CH:10][CH:9]=1)[Si:19]([CH3:21])([CH3:20])[CH3:18]
Reactant: C[Si](C)(C)Cl
Reactant: C=Cc1ccc(N[Si](C)(C)C)cc1
Agent: CC[Mg]Br
Solvent: C1CCOC1
Product: C=Cc1ccc(N([Si](C)(C)C)[Si](C)(C)C)cc1
Yield: 55 %

Procedure:
To a solution of ethylmagnesium bromide in THF (0.6M, 150 mL) was added dropwise 4-[N-(trimethylsilyl)amino]styrene (8.4 g, 44 mmole) with stirring. The mixture was stirred at 40° C. for 16 hours. To the resulting solution was added trimethylsilylchloride (13 g, 120 mmole)and the mixture stirred at room temperature for 6 hours. By fractional distillation, a product was isolated at 45°-48° C./0.32 mm in 55% yield. The product was confirmed by spectral analysis to be the desired compound.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:24](=[CH:25][CH:26]=1)[C:8]1=[N:9][O:10][C:11]([C:12]3[CH:13]=[CH:14][C:15]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([CH:19]=3)[C:17]#[N:18])=[C:7]1[CH2:6][CH2:5]2.[CH2:27]([Sn](CCCC)(CCCC)C=C)[CH2:28]CC.[Cl-].[Li+]>O1CCOCC1.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>[CH:21]([O:20][C:15]1[CH:14]=[CH:13][C:12]([C:11]2[O:10][N:9]=[C:8]3[C:24]4[C:4]([CH2:5][CH2:6][C:7]=23)=[CH:3][C:2]([CH:27]=[CH2:28])=[CH:26][CH:25]=4)=[CH:19][C:16]=1[C:17]#[N:18])([CH3:22])[CH3:23]
Reactant: CC(C)Oc1ccc(-c2onc3c2CCc2cc(Br)ccc2-3)cc1C#N
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1COCCO1
Product: C=Cc1ccc2c(c1)CCc1c-2noc1-c1ccc(OC(C)C)c(C#N)c1
Temperature: 100 °C
Yield: 67.3 %

Procedure:
5-(7-Bromo-4,5-dihydronaphtho[1,2-c]isoxazol-3-yl)-2-isopropoxybenzonitrile (Preparation 15B, 0.15 g, 0.367 mmol) dissolved in dioxane (3 mL) was transferred to a 15 mL sealed tube. Tributyl(vinyl)stannane (0.118 mL, 0.403 mmol) was added followed by lithium chloride (0.047 g, 1.100 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.042 g, 0.037 mmol). The contents were purged with nitrogen gas for 5 min., immersed in an oil bath, and heated at 100° C. for 14 h. The reaction mixture was concentrated and to the red-brown oil was added ethyl acetate (10 mL). The contents were sonicated for 5 min. and filtered. The filter cake was washed with ethyl acetate (2×5 mL). The filtrate was concentrated under reduced pressure and the resulting oil was subjected to silica gel column chromatography (hexane/ethyl acetate). Fractions corresponding to the product were collected and concentrated to yield 2-isopropoxy-5-(7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazol-3-yl)benzonitrile (0.088 g, 0.247 mmol, 67% yield) as a pale yellow solid. LC/MS M+1=357.1.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1.Br[CH2:23][C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH3:37])[CH:25]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH2:23][C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH3:37])[CH:25]=1)[C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: CCOC(=O)COc1ccc(CBr)cc1C
Reactant: COCCNc1cccc(-c2ccc(C(F)(F)F)cc2)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CCOC(=O)COc1ccc(CN(CCOC)c2cccc(-c3ccc(C(F)(F)F)cc3)c2)cc1C
Reaction time: 3 h
Yield: 52.8 %

Procedure:
To a solution of N-(2-methoxyethyl)-N-[4′-(trifluoromethyl)-1,1′-biphenyl-3-yl]amine (0.1 g, 0.34 mmol) in anhydrous acetonitrile (10 mL) was added ethyl [4-(bromomethyl)-2-methylphenoxy]acetate (0.097 g, 0.34 mmol) and N,N-diisopropylethylamine (0.059 mL, 0.34 mmol). The resulting mixture was heated to reflux and stirred under nitrogen for 3 h. The reaction mixture was concentrated in vacuo and the residue partitioned between water (20 mL) and CH2Cl2 (40 mL), the organic extract was separated by hydrophobic frit and the solvents removed in vacuo. Purification by Biotage™ chromatography (Silica, 12 g) eluting 9:1 cyclohexane:EtOAc afforded the title compound as a colourless oil (90 mg).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH:4]=[O:5].Cl.Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>C(#N)C>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:2]([O:1][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[C:3]([CH:6]=1)[CH:4]=[O:5]
Reactant: ClCCN1CCCCC1
Reactant: COc1ccc(O)c(C=O)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC#N
Product: COc1ccc(OCCN2CCCCC2)c(C=O)c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 41.8 %

Procedure:
A mixture of 2-hydroxy-5-methoxybenzaldehyde (0.761 g, 5 mmol), 1-(2-chloroethyl)piperidine hydrochloride (0.921 g, 5.00 mmol), K2CO3 (2.07 g, 14.99 mmol), and sodium iodide (0.075 g, 0.50 mmol) in acetonitrile (40 mL) was stirred at 100° C. overnight. The reaction was allowed to cool to ambient temperature and sat'd aqueous K2CO3 was added to the reaction mixture. The mixture was poured into a separatory funnel and extracted with EtOAc. The organic phase was dried over anhydrous MgSO4, filtered through a bed of Celite, and conc. in vacuo to yield the product which was purified via silica gel chromatography (80 g) using EtOAc/hexanes (4:1) as eluent to yield the title compound as a brown oil (0.551 g, 42%); m/z 264.
Reaction SMILES: [CH3:1][O:2][N:3]=C1C2C=CN=NC=2OC1.[F:13][C:14]([F:26])([F:25])[C:15]1[CH:20]=[CH:19][N:18]=[C:17]2[O:21][CH2:22][C:23](=O)[C:16]=12>>[CH3:1][O:2][N:3]=[C:23]1[C:16]2[C:17](=[N:18][CH:19]=[CH:20][C:15]=2[C:14]([F:26])([F:25])[F:13])[O:21][CH2:22]1
Reactant: CON=C1COc2nnccc21
Reactant: O=C1COc2nccc(C(F)(F)F)c21
Product: CON=C1COc2nccc(C(F)(F)F)c21

Procedure:
This compound was prepared using a method analogous to that of furo[2,3-c]pyridazin-5(6H)-one O-methyl oxime (A.2.3.3), 4-(trifluoromethyl)furo[2,3-b]pyridin-3(2H)-one replacing furo[2,3-c]pyridazin-5(6H)-one. Purification by (KP-SIL™ from Biotage) using Hept/EtOAc (9/1) gives the desired product as colorless foam;