Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:14])[CH2:10][CH2:11][CH2:12][CH3:13])=[CH:5][CH:4]=1.[N:15]([O-])=[O:16].[Na+]>C1COCC1.C(OCC)C>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([C:9](=[O:14])/[C:10](=[N:15]\[OH:16])/[CH2:11][CH2:12][CH3:13])=[CH:7][CH:8]=1
Reactant: CCCCC(=O)c1ccc(Br)cc1
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCC/C(=N/O)C(=O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 59.1 %

Procedure:
The conc. HCl (40 mL) was added dropwise to a solution of 1-(4-bromophenyl)pentan-1-one (4.68 g, 19.41 mmol) and sodium nitrite (4.02 g, 58.2 mmol) in THF (80 ml) at 0° C. and allowed to warm to room temperature and stirred 18 hours. The reaction mixture was diluted with diethyl ether and the organic phase washed with sat'd NaHCO3 and brine. Concentration gave (Z)-1-(4-bromophenyl)-2-(hydroxyimino)pentan-1-one 3.1 g (33%) as an oil which was used without further purification.). RT=2.1 min, (Condition 1) LCMS: Anal. Calcd. for C11H12BrN1O2 270.01. found: 270.15 (M+H)+.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:10]1[C:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[C:12]2[C:17](=[CH:18][C:19]=1[CH3:20])[N:16]=[C:15](C1NN=CC=1)[CH:14]=[CH:13]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:41]2[CH:42]=[N:43][NH:44][CH:45]=2)O1>>[C:1]([O:5][C@@H:6]([C:10]1[C:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[C:12]2[C:17](=[CH:18][C:19]=1[CH3:20])[N:16]=[C:15]([C:41]1[CH:42]=[N:43][NH:44][CH:45]=1)[CH:14]=[CH:13]2)[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: Cc1cc2nc(-c3ccn[nH]3)ccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Product: Cc1cc2nc(-c3cn[nH]c3)ccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Reaction time: 1 h

Procedure:
(S)-2-tert-Butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-(1H-pyrazol-4-yl)quinolin-6-yl)acetic acid (77) was prepared following the procedure for (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-(1H-pyrazol-5-yl)quinolin-6-yl)acetic acid of Example 70 except that 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole was used instead of 1H-pyrazol-5-ylboronic acid and the in the final step the reaction was stirred for 1 hour. 1H-NMR: 400 MHz, (CD3CN) δ: 8.45 (s, 2 H), 8.08 (s, 1 H), 7.89 (d, J=8.8 Hz, 1 H), 7.73 9 (d, J=8.8 Hz, 1 H), 7.59 (m, 3 H), 7.34 (d, J=7.2 Hz, 1H), 5.22 (s, 1 H), 2.63 (s, 3 H), 0.97 (s, 9 H). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H25ClN3O3: 450.15. found: 450.53.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][N:14]([CH3:35])[C:15](=N)[CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH2:20][CH2:19]1)[CH2:6]2.[BH4-].[BH4-].[BH4-].[BH4-].[Na+].[Na+].[Na+].[Na+].[OH-].[Na+].ClCCl>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][N:14]([CH3:35])[CH2:15][CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH2:20][CH2:19]1)[CH2:6]2
Reactant: COc1cc2c(cc1OC)CC(=O)N(CCC(=N)N(C)C[C@H]1Cc3cc(OC)c(OC)cc31)CC2
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: COc1cc2c(cc1OC)CC(=O)N(CCCN(C)C[C@H]1Cc3cc(OC)c(OC)cc31)CC2
Reaction time: 8 h
Yield: 102.8 %

Procedure:
1 g of the product obtained in Step 1 (containing 46% amidine) is dissolved in 15 mL of methanol and then 86 mg (2.26 mmol, 1.2 equivalents) of sodium tetraborohydride are added at ambient temperature. Stirring is carried out overnight at ambient temperature, and then 5 mL of 20% aqueous sodium hydroxide solution and 20 mL of dichloromethane are added. Vigorous stirring is carried out for 15 minutes. The organic phase is then extracted, washed with water, dried over MgSO4, filtered and then evaporated to dryness. There is obtained 1 g of an oil which is purified by flash chromatography on 100 g of silica (eluant=dichloromethane/ethanol/NH4OH: 90/10/1) to yield 210 mg of the title product in the form of an oil.
Reaction SMILES: Cl[C:2]1[N:3]([CH2:10][C:11]([CH3:31])([OH:30])[CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([O:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[H-].[Na+].C(OCC)(=O)C>CN(C=O)C>[CH3:31][C:11]1([CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([O:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)[O:30][C:2]2=[N:6][C:5]([N+:7]([O-:9])=[O:8])=[CH:4][N:3]2[CH2:10]1
Reactant: CC(O)(CN1CCC(Oc2ccc(C(F)(F)F)cc2)CC1)Cn1cc([N+](=O)[O-])nc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC1(CN2CCC(Oc3ccc(C(F)(F)F)cc3)CC2)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 0 °C
Reaction time: 1 h
Yield: 38.3 %

Procedure:
To a solution of 1-(2-chloro-4-nitroimidazol-1-yl)-2-methyl-3-[4-(4-trifluoromethylphenoxy)-piperidin-1-yl]propan-2-ol prepared in Example 230 (225 mg, 0.49 mmol) in DMF (2.5 ml), sodium hydride (23 mg, 0.59 mmol) was added followed by stirring for 1 hour with cooling on ice-bath. To the reaction mixture, ice-water and ethyl acetate were added. The precipitates were filtered off, washed with water, recrystallized from methylene chloride-diisopropyl ether and then washed with n-hexane to afford 2-methyl-6-nitro-2-[4-(4-trifluoromethylphenoxy)piperidin-1-ylmethyl]-2,3-dihydroimidazo[2,1-b]oxazole (80 mg, yield 39%) as a light yellow solid.
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[C:7]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Br:20])[NH:8][C:9](=[O:12])[C:10]=1[OH:11])=[O:4].[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH2:27])=[CH:24][CH:23]=1>>[F:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH:27][C:3]([C:5]2[N:6]=[C:7]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Br:20])[NH:8][C:9](=[O:12])[C:10]=2[OH:11])=[O:4])=[CH:24][CH:23]=1
Reactant: COC(=O)c1nc(Cc2ccccc2Br)[nH]c(=O)c1O
Reactant: NCc1ccc(F)cc1
Product: O=C(NCc1ccc(F)cc1)c1nc(Cc2ccccc2Br)[nH]c(=O)c1O
Yield: 70.6 %

Procedure:
The compound was prepared according to the same procedure as in Example 21 using 2-(2-bromo-benzyl)-5-hydroxy-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid methyl ester (0.08 g; 0.236 mmol) and 4-fluorobenzylamine (0.5 ml; 4.4 mmol). This gave the title compound as a white solid (0.072 g; 70%). LCMS: m/z=433 (MH+).
Reaction SMILES: Br[CH2:2][C:3]#[N:4].[C:5]1(=[O:15])[NH:9][C:8](=[O:10])[C:7]2=[CH:11][CH:12]=[CH:13][CH:14]=[C:6]12.[K].O>CN(C)C=O>[O:10]=[C:8]1[C:7]2[C:6](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5](=[O:15])[N:9]1[CH2:2][C:3]#[N:4]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: N#CCBr
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: N#CCN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 79.4 %

Procedure:
To a solution of bromoacetonitrile (22 g) in N,N-dimethylformamide (200 mL) was added potassium phthalimide (34 g) under ice-cooling, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound as white crystals (yield 27 g, 80%).
Reaction SMILES: [CH3:1][CH2:2][C:3]1[C:12]2[CH2:13][N:14]3[C:19](=[O:20])[C:18]4[CH2:21][O:22][C:23]([C@:25]([OH:28])([CH2:26][CH3:27])[C:17]=4[CH:16]=[C:15]3[C:11]=2[N:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([N:38]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]3)[CH2:34][CH2:33]1)=[O:31])[CH:7]=[CH:8]2)=[O:24].C([O-])(=[O:46])C.C([OH:50])C.[ClH:51].CCCCCCC>C(OCC)(=O)C>[CH3:1][CH2:2][C:3]1[C:12]2[CH2:13][N:14]3[C:19](=[O:20])[C:18]4[CH2:21][O:22][C:23]([C@:25]([OH:28])([CH2:26][CH3:27])[C:17]=4[CH:16]=[C:15]3[C:11]=2[N:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([O:29][C:30]([N:32]1[CH2:33][CH2:34][CH:35]([N:38]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]3)[CH2:36][CH2:37]1)=[O:31])[CH:7]=[CH:8]2)=[O:24].[OH2:46].[OH2:50].[OH2:20].[ClH:51]
Reactant: CCO
Reactant: CC(=O)[O-]
Agent: CCc1c2c(nc3ccc(OC(=O)N4CCC(N5CCCCC5)CC4)cc13)-c1cc3c(c(=O)n1C2)COC(=O)[C@]3(O)CC
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: O
Temperature: 70 °C
Reaction time: 1 h

Procedure:
To a suitable vessel were charged amorphous irinotecan acetate (6.35 g) and ethanol (45 mL). The resulting mixture was heated to reflux (about 70° C.) and remained as a suspension. 2N HCl (5.4 mL) was added to the reaction mixture to adjust the pH to less than 4. N-heptane (25 mL) and ethanol (30 mL) were added to the resulting mixture. The solution was then cooled to 0˜10° C. and stirred at this temperature for 1 hour, and then charged with 200 mL of ethyl acetate in order to perform a solvent swap. The solution was then filtrated and washed with ethyl acetate (50 mL). The solid was dried in vacuum. Due to a lower than expected water content, the solid was heated under high humidity for one hour and then cooled to give irinotecan hydrochloride trihydrate Form I (6.6 g).
Reaction SMILES: N1CCOCC1.BrC1SC(C=O)=CC=1.[N:15]1([C:21]2[S:25][C:24]([CH:26]=O)=[CH:23][CH:22]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[O:39][CH3:40])[CH2:33][C:34]#[N:35]>>[CH3:28][O:29][C:30]1[CH:31]=[C:32](/[C:33](=[CH:26]/[C:24]2[S:25][C:21]([N:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)=[CH:22][CH:23]=2)/[C:34]#[N:35])[CH:36]=[CH:37][C:38]=1[O:39][CH3:40]
Reactant: COc1ccc(CC#N)cc1OC
Reactant: O=Cc1ccc(N2CCOCC2)s1
Agent: O=Cc1ccc(Br)s1
Solvent: C1COCCN1
Product: COc1ccc(/C(C#N)=C/c2ccc(N3CCOCC3)s2)cc1OC
Yield: 14.8 %

Procedure:
Through the procedure as employed in Production step 1, an amine moiety derived from morpholine (523 mg) was introduced into 5-bromothiophene-2-carboxaldehyde (382 mg), to thereby yield 5-morpholin-4-yl-thiophene-2-carbaldehyde (yield: 176 mg, 45%). The produced 5-morpholin-4-yl-thiophene-2-carbaldehyde (172 mg) was condensed with 3,4-dimethoxybenzyl cyanide (154 mg) through Method A (production step 2), to thereby yield the target product (yield: 46 mg, 15%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[CH:13]2)=[CH:4][CH:3]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][CH:33]=[C:34]([CH2:36]Cl)[N:35]=2)=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][CH:33]=[C:34]([CH2:36][O:1][C:2]3[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]4[CH:16]=[CH:15][N:14]=[CH:13]4)=[CH:4][CH:3]=3)[N:35]=2)=[CH:27][CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: ClCc1coc(-c2ccc(OCc3ccccc3)cc2)n1
Reactant: Oc1ccc(CCCCn2ccnc2)cc1
Product: c1ccc(COc2ccc(-c3nc(COc4ccc(CCCCn5ccnc5)cc4)co3)cc2)cc1
Yield: 54 %

Procedure:
In substantially the same manner as in Working Example 109, 1-[4-(4-hydroxyphenyl)butyl]imidazole was allowed to react with 2-(4-benzyloxyphenyl)-4-chloromethyloxazole to give 2-(4-benzyloxyphenyl)-4-[4-[4-(1-imidazolyl)butyl]phenoxymethyl]oxazole. The yield was 54%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 118-120° C.
Reaction SMILES: [NH2:1][C:2]1[C:7](I)=[CH:6][N:5]=[C:4]([Br:9])[CH:3]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[NH2:1][C:2]1[CH:3]=[C:4]([Br:9])[N:5]=[CH:6][C:7]=1/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: Nc1cc(Br)ncc1I
Reactant: C=CC(=O)OCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)/C=C/c1cnc(Br)cc1N
Temperature: 100 °C
Yield: 89.6 %

Procedure:
4-Amino-2-bromo-5-iodopyridine (9.0 g 30.0 mmole) was dissolved in DMF (90 mL) and ethyl acrylate (6.5 mL, 60 mmole), triethylamine (6.1 mL, 43.2 mmole), tri-o-tolylphosphine (728 mg 2.4 mmole) and palladium acetate (270 mg 1.2 mmole) were added. The reaction was placed under nitrogen and heated at 100° C. for 3 hours. The reaction was concentrated in vacuo and diluted with EtOAc (250 mL). Water (100 mL) was added and the biphasic mixture filtered through celite. The filter cake was washed with EtOAc and the organic layers collected. The combined organic layers were washed with water (2×100 mL), brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a gradient of 10-40% EtOAc in DCM to afford the title compound (7.29 g, 89%).
Reaction SMILES: Cl[C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[SH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22].CC(C)([O-])C.[K+].Cl>CN(C=O)C>[F:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]([C:5]2[CH:16]=[CH:17][C:2]([S:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[N:3][CH:4]=2)=[O:7])=[CH:10][CH:11]=1
Reactant: O=C(O)CCS
Reactant: O=C(Nc1ccc(F)cc1)c1ccc(Cl)nc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)CCSc1ccc(C(=O)Nc2ccc(F)cc2)cn1
Temperature: 60 °C
Yield: 66.3 %

Procedure:
To a solution of 6-chloro-N-(4-fluorophenyl)nicotinamide (0.20 g, 0.80 mmol) in 10 mL of DMF was added 3-mercaptopropionic acid (0.10 mL, 1.2 mmol) and potassium tert-butoxide (0.31 g, 2.8 mmol) and the mixture heated to 60° C. After 9 h the reaction mixture was poured into ice water, HCl (1 M, aq) added to adjust to pH 6, and the solids removed via filtration. The filtrate was then taken to pH 10 with NaOH (4M, aq) and extracted with ethyl acetate. HCl (6M, aq) was then added to the filtrate to adjust the pH to 4 and extracted with ethyl acetate, dried over sodium sulfate, and the solvents removed in vacuo to yield a white solid. Purification by recrystallization using ethyl acetate gave 0.17 g (66%) of the titled product as a white solid; MS (EI) m/z 319.20 (M−H)−.
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].CI.[F:9][C:10]([F:42])([F:41])[C:11]1[CH:12]=[C:13]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:14][O:15][CH2:16][C:17]([OH:33])([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][CH2:19][NH:20][C:21](=[O:26])[C:22]([F:25])([F:24])[F:23]>CC(C)=O>[F:9][C:10]([F:41])([F:42])[C:11]1[CH:12]=[C:13]([CH:34]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:36]=1)[CH2:14][O:15][CH2:16][C:17]([OH:33])([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][CH2:19][N:20]([CH3:1])[C:21](=[O:26])[C:22]([F:24])([F:25])[F:23]
Reactant: O=C([O-])[O-]
Reactant: O=C(NCCC(O)(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1)C(F)(F)F
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: CN(CCC(O)(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1)C(=O)C(F)(F)F
Temperature: 60 °C

Procedure:
Excess amount of potassium carbonate (150 mg, 1.1 mmol) and excess amount of methyl iodide (0.040 ml, 0.064 mmol) were mixed with N-(4-(3,5-bis(trifluoromethyl)benzyloxy)-3-hydroxy-3-phenylbutyl)-2,2,2-trifluoroacetamide (15 mg, 0.030 mmol) in acetone (2 ml). The reaction mixture was heated in microwave at 60° C. for 10 minutes. The salt precipitate was filtered off and the filtrate was concentrated. The residue was purified by preparative HPLC to give the desired N-methylacetamide. 1H NMR (300 MHz, MeOH) δ ppm 7.84 (s, 3 H) 7.46–7.54 (m, 2 H) 7.35 (ddd, J=8.14, 6.50, 4.76 Hz, 2 H) 7.22–7.30 (m, 1 H) 4.61–4.73 (m, 2 H) 3.62–3.75 (m, 2 H) 3.40–3.55 (m, 1 H) 3.11–3.37 (m, 1 H) 3.01 (s, 2 H) 2.93 (s, 1 H) 2.15–2.31 (m, 2 H); LRMS [ESI, (MH+−H2O)] m/z calcd for C22H19NO2F9 500.13, found 499.97.
Reaction SMILES: [O:1]1[CH2:7][CH:6]([CH2:8][NH2:9])[CH2:5][O:4][C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2.[S:14](N)([NH2:17])(=[O:16])=[O:15].C(Cl)(Cl)Cl>O1CCOCC1>[O:1]1[CH2:7][CH:6]([CH2:8][NH:9][S:14]([NH2:17])(=[O:16])=[O:15])[CH2:5][O:4][C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2
Reactant: NCC1COc2ccccc2OC1
Reactant: NS(N)(=O)=O
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Product: NS(=O)(=O)NCC1COc2ccccc2OC1

Procedure:
((3,4-Dihydro-2H-benzo[b][1,4]dioxepin-3-yl)methyl)amine (2.90 g, 16.2 mmol) and sulfamide (3.11 g, 32.4 mmol) were combined in dry dioxane (60 ml) and heated to reflux overnight. Chloroform was added and the precipitate was removed by filtration. The filtrate was concentrated under vacuum and purified by chromatography (2% to 8% acetone in dichloromethane) to yield the title compound as an off-white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[CH:4]2O[CH:3]12.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[NH:27][CH:26]=[N:25][CH:24]=2)=[CH:19][CH:18]=1>>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[N:27]([C:4]3[C:5]4[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=4)[O:11][C:2]([CH3:15])([CH3:1])[CH:3]=3)[CH:26]=[N:25][CH:24]=2)=[CH:21][CH:22]=1
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Reactant: Clc1ccc(-c2cnc[nH]2)cc1
Product: CC1(C)C=C(n2cncc2-c2ccc(Cl)cc2)c2cc(C#N)ccc2O1

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and 5-(4-chloro-phenyl)-1H-imidazole as starting materials, the title compounds were prepared as white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[C:12]([C:28]([NH:30][CH3:31])=[O:29])[C:13](=[O:27])[N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)[C:15]=2[CH3:16])=[CH:4][CH:3]=1.C(O)=[O:33]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:10]2[CH:11]=[C:12]([C:28]([NH:30][CH3:31])=[O:29])[C:13](=[O:27])[N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)[C:15]=2[CH3:16])=[O:33])=[CH:4][CH:3]=1
Reactant: CNC(=O)c1cc(C#Cc2ccc(Cl)cc2)c(C)n(-c2cccc(C(F)(F)F)c2)c1=O
Reactant: O=CO
Product: CNC(=O)c1cc(C(=O)Cc2ccc(Cl)cc2)c(C)n(-c2cccc(C(F)(F)F)c2)c1=O
Temperature: 120 °C
Yield: 66 %

Procedure:
5-[(4-Chlorophenyl)ethynyl]-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (111 mg, 0.25 mmol) was mixed with formic acid (1 ml) and heated in a microwave oven to 120° C. for 1 h. The formic acid was evaporated off and the residue was purified on an Xterra C8 column using a gradient of acetonitrile/water. Freeze drying of the mixture afforded 5-[(4-chlorophenyl)acetyl]-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (77 mg, 66%).
Reaction SMILES: [C:1]1(/[C:7](/[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:8]\[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]1([N:27]=[C:28]=[S:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(N(CC)CC)C>[C:21]1([NH:27][C:28]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]/[CH:8]=[C:7](\[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)/[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[S:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: S=C=Nc1ccccc1
Reactant: OCCCCC/C=C(\c1ccccc1)c1cccnc1
Solvent: CCN(CC)CC
Product: S=C(Nc1ccccc1)OCCCCC/C=C(\c1ccccc1)c1cccnc1

Procedure:
In the presence of triethylamine, (E)-7-phenyl-7-(3-pyridyl)-6-hepten-1-ol (2.0 g, 7.4 mmoles) was reacted with phenyl isothiocyanate (1.0 g, 7.5 mmoles) in the same manner as Example 9 to give 1-phenylaminothiocarbonyloxy-(E)-7-phenyl-7-(3-pyridyl)-6-heptene (Compound Id-28, 2.2 g) as crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][CH3:12])=[O:10].CN(C)/C=C(\C1C=CC=CC=1C)/[C:17](OC)=[O:18]>>[OH:18]/[CH:17]=[C:8](/[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])\[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)Cc1ccccc1C
Reactant: COC(=O)/C(=C/N(C)C)c1ccccc1C
Product: COC(=O)/C(=C\O)c1ccccc1C

Procedure:
In a similar to manner to Example 1, methyl (2-methylphenyl)acetate was converted to methyl (E)-3-dimethylamino-2-(2-methylphenyl)prop-2-enoate, bp 125°-7°/0.1 mm, which on cooling gave a crystalline solid, mp 48°-49°. This was then hydrolysed in a similar manner to Example 1, but using Amberlite IR 120 resin instead of Amberlyst 15, to give methyl (Z)-3-hydroxy-2-(2-methylphenyl)prop-2-enoate, obtained as an oil and which had the following nmr spectral data: 2.15(3H,s,Me), 3.67(3H,s,CO2Me), 7.0-7.4(5H,m,ArH and =CH), 11.8(1H,d,OH)
Reaction SMILES: C(OC1C=CC(C(C2C=CC=CC=2)=O)=CC=1)C=C.[CH3:19][SiH:20]([CH3:25])[O:21][SiH:22]([CH3:24])[CH3:23].C(OC1C=CC(C(C2C=CC=CC=2)=O)=CC=1)C=C.C1COCC1>C1COCC1>[CH3:19][SiH:20]([CH3:25])[O:21][Si:22]([CH3:24])([CH3:23])[O:21][SiH:20]([CH3:25])[CH3:19]
Reactant: C[SiH](C)O[SiH](C)C
Agent: C=CCOc1ccc(C(=O)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C[SiH](C)O[Si](C)(C)O[SiH](C)C
Temperature: 60 °C
Reaction time: 0.25 h

Procedure:
Allyloxybenzophenone 1 (200 g, 840 mmol) was dissolved with warming in THF (150 mL, EM Science) and charged to an addition funnel placed on a 2L four-necked flask equipped with a mechanical stirrer, reflux condenser and internal temperature probe under a dry air purge. To the reaction vessel was added 1,1,3,3-tetramethyldisiloxane (740 mL, 4.18 mol, Hanse Chemie) and THF (100 mL). The internal pot temperature was raised to 50° C., at which point chlorotris(triphenylphosphine) rhodium (“Wilkinson's catalyst”, 22 mg, 11 ppm based on mass of allyloxybenzophenone 1, Aldrich Chemcial) was added to the pot along with a portion (5 mL) of the 4-allyloxybenzophenone/THF solution. The internal reaction temperature was raised to 60° C., at which point the 4-allyloxybenzophenone solution was added to the reactor pot over the course of 45 min. The internal temperature of the reaction was held between 60–65° C. during the course of the addition, which is exothermic. After the addition was complete, the reaction was stirred at 60° C. for an additional 15 min., at which point no starting material was present by GC analysis. The reaction was allowed to cool to 35° C., and activated carbon (3 lab scoops, Aldrich Chemical) was added. The resulting slurry was stirred for 30 min., then filtered to yield a pale yellow solution. Solvent was removed from the product in vacuo to yield a yellow oil (329 g, 104% due to presence of ˜10 mol % 1,1,3,3,5,5-hexamethyltrisiloxane in the commercial grade 1,1,3,3-tetramethyldisiloxne starting material; i.e. the reaction is essentially quantitative). The product exhibited acceptable 1H, 13C & 29Si NMR, UV-Vis and FT-IR spectral characteristics.
Reaction SMILES: [CH:1]1([N:6]2[C:10]([NH:11][C:12]3[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:14](O)=O)=[CH:9][CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+].[OH-].O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:14]1[C:13]2[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]=[C:10]2[N:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[N:7]=[CH:8][C:9]=12
Reactant: O=C(O)c1ccccc1Nc1ccnn1C1CCCC1
Reactant: O=P(Cl)(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Product: Clc1c2ccccc2nc2c1cnn2C1CCCC1

Procedure:
A mixture of N-(1-cyclopentylpyrazol-5-yl) anthranilic acid (21 g, 0.0775 mol) and POCl3 (100 ml) is refluxed for 8 hours. The reaction mixture is poured into ice waterl and neutralized with NH4OH. A gum forms which is extracted with CH2Cl2. The CH2Cl2 layer is then washed with water, dried over MgSO4, filtered and concentrated. The residue is purified by column chromatography on silica gel eluting with 40% to 70% CH2Cl2 /hexane to afford 7.5 g of 4-chloro-1-cyclopentyl-1H-pyrazolo[3,4-b]quinoline, m.p. 97°-98° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.S(Cl)([Cl:15])=O.C1(C)C=CC=CC=1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([Cl:15])=[O:12])=[CH:4][CH:3]=1
Reactant: O=C(O)CCc1ccc(F)cc1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: O=C(Cl)CCc1ccc(F)cc1
Reaction time: 24 h
Yield: 86.8 %

Procedure:
3-(para-Fluorophenyl)propionic acid (25.00 g, 150.0 mmol, 1 eq.) was dissolved in methylene chloride (100 mL) at 25° C. under N2 and thionyl chloride (54.2 mL, 740.0 mmol, 5 eq.) added dropwise via an addition funnel. Worked up after 24 hours by stripping off the solvent then rerotovaping 2 times from toluene (25 mL) to obtain 24.3 g of a yellow oil.