Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:3][NH:4][C:5](=[O:26])[CH:6]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=1)[CH2:7][CH:8]([CH3:10])[CH3:9])#[N:2].Br[C:28]1[CH:42]=[CH:41][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].CN(C=O)C>O.[Pd](Cl)Cl>[C:1]([CH2:3][NH:4][C:5]([CH:6]([C:11]1[CH:12]=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[CH:41][CH:42]=2)[CH:14]=[CH:15][CH:16]=1)[CH2:7][CH:8]([CH3:9])[CH3:10])=[O:26])#[N:2]
Reactant: CC(C)CC(C(=O)NCC#N)c1cccc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: CC(C)(C)OC(=O)NCc1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)CC(C(=O)NCC#N)c1cccc(-c2ccc(CNC(=O)OC(C)(C)C)cc2)c1
Temperature: 82.5 °C
Yield: 82.1 %

Procedure:
A mixture comprised of N-cyanomethyl-4-methyl-2-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]pentanamide (250 mg, 0.702 mmol), tert-butyl 4-bromobenzylcarbamate (303 mg, 1.053 mmol), sodium bicarbonate (1.1 mL, 2.11 mmol), palladium(II) chloride (18 mg, 0.0211 mmol) and DMF (15.8 mL) was stirred under nitrogen at between 80-85° C. until the reaction was complete. The mixture was diluted with water and the product was extracted with diethyl ether (3×). The combined extracts were washed with brine, dried (MgSO4) and then concentrated in vacuo. The product was purified from the residue by flash chromatography over silica gel (ethyl acetate/hexanes) to provide tert-butyl 3′-(1-cyanomethylcarbamoyl-3-methylbutyl)biphenyl-4-ylmethylcarbamate (252 mg, 0.576 mmol). 1H NMR (400 MHz, d6-DMSO): δ 8.79 (br s, 1H), 7.58-7.26 (m, 9H), 4.16 (d, J=5.2 Hz, 2H), 4.11 (br s, 2H), 3.67 (dd, J=7.2, 7.2 Hz, 1H), 1.95-1.91 (m, 1H), 1.57-1.53 (m, 1H), 1.40-1.33 (m, 10H), 0.88 (dd, J=6.7, 6.7 Hz, 6H); MS (−ESI) m/z 434.6 (M−H)−.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:25][C:15]2[NH:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][C:22]=3[C:14]=2[CH2:13]1.Br[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C=O)C>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH:12]1[CH2:25][C:15]2[N:16]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[N:29]=3)[C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][C:22]=3[C:14]=2[CH2:13]1
Reactant: N#Cc1ccc2[nH]c3c(c2c1)CC(N1C(=O)c2ccccc2C1=O)C3
Reactant: Fc1cccc(CBr)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: N#Cc1ccc2c(c1)c1c(n2Cc2cccc(F)n2)CC(N2C(=O)c3ccccc3C2=O)C1
Yield: 88.4 %

Procedure:
Dissolve (±)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1,2,3,4-tetrahydro-cyclopenta[b]indole-7-carbonitrile (6.88 g, 21.0 mmol) and 2-bromomethyl-6-fluoro-pyridine (3.99 g, 21.0 mmol) in DMF (80 mL). Add cesium carbonate (7.51 g, 23.1 mmol, 1.10 equivalents) and stir the reaction mixture at room temperature under nitrogen for 48 h. Dilute the reaction with ethyl acetate, wash with water (3×), dry over anhydrous sodium sulfate, filter, and concentrate to obtain a semi-solid (8.10 g). Purify the crude product on a 120 g silica gel column eluting with 0 to 100% ethyl acetate/hexanes to obtain 6.7 g of a tan/brown solid. Suspend the product in ether (100 mL) at room temperature overnight. Filter the solid, rinse with ether, and dry under high vacuum to obtain the title compound as a tan solid (5.70 g, 62%). LCMS 437.1 (M+1).
Reaction SMILES: Cl.[CH3:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.Br[C:20]1[CH:32]=[CH:31][C:23]([CH2:24][CH2:25][C:26]2[NH:30][N:29]=[N:28][N:27]=2)=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O>[CH3:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:20]2[CH:21]=[CH:22][C:23]([CH2:24][CH2:25][C:26]3[NH:30][N:29]=[N:28][N:27]=3)=[CH:31][CH:32]=2)=[CH:12][CH:11]=1
Reactant: Brc1ccc(CCc2nnn[nH]2)cc1
Reactant: C[C@@H]1CCCN1CCc1ccc(B(O)O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: C[C@@H]1CCCN1CCc1ccc(-c2ccc(CCc3nnn[nH]3)cc2)cc1
Temperature: 130 °C

Procedure:
A mixture of (R)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)phenylboronic acid hydrochloride (50 mg, 0.185 mmol), 5-(4-bromophenethyl)-1H-tetrazole (56.3 mg, 0.223 mmol), Na2CO3 (79 mg, 0.742 mmol), and dichlorobis(p-dimethylaminophenyldi-tert-butylphosphine)palladium (1.313 mg, 1.855 μmol) in 1,4-dioxane (1 mL) and H2O (0.2 mL) was heated under microwave irradiation at 130° C. for 120 min. The mixture was concentrated and the residue was purified by HPLC to give the title compound. LCMS m/z=362.5 [M+H]+; 1.22-1.31 (m, 0.4H), 1.45 (d, J=6.6 Hz, 2.6H), 1.69-1.82 (m, 1H), 2.00-2.10 (m, 2H), 2.21-2.32 (m, 1H), 3.04-3.20 (m, 6H), 3.25-3.31 (m, 2H), 3.35-3.47 (m, 1H), 3.50-3.60 (m, 1H), 3.72-3.83 (m, 1H), 7.31 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 7.56 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.2 Hz, 2H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([C:19]#[N:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30](=[O:50])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[C:41]([CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)=[CH:40][N:39]=[N:38]2)[CH:32]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([C:19]#[N:20])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30](=[O:50])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[C:41]([CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)=[CH:40][N:39]=[N:38]2)[CH:32]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2nncc2COC2CCCCO2)c1
Reactant: CC(C)(C)OC(=O)Nc1cc(N2CCCC2)c(C#N)cc1N
Product: CC(C)(C)OC(=O)Nc1cc(N2CCCC2)c(C#N)cc1NC(=O)CC(=O)c1cccc(-n2nncc2COC2CCCCO2)c1

Procedure:
The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-1-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light orange foam (380 mg, 60%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[CH3:34][C:35]1[C:36]([CH:44]2[CH2:49][CH2:48][N:47]([CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH2:46][CH2:45]2)=[CH:37][C:38]([O:42][CH3:43])=[C:39]([CH:41]=1)[NH2:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.C[O-].[Na+]>C(Cl)Cl>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:40][C:39]3[CH:41]=[C:35]([CH3:34])[C:36]([CH:44]4[CH2:45][CH2:46][N:47]([CH2:50][CH2:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:49]4)=[CH:37][C:38]=3[O:42][CH3:43])[N:7]=2)[CH:18]=1
Reactant: COc1cc(C2CCN(CCS(C)(=O)=O)CC2)c(C)cc1N
Reactant: O=C(Nc1c(F)cccc1F)c1cccc(-c2nc3ccccn3c2-c2ccnc(Cl)n2)c1
Agent: C[O-]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Solvent: OCC(F)(F)F
Solvent: ClCCl
Product: COc1cc(C2CCN(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
Temperature: 150 °C
Yield: 43.6 %

Procedure:
3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (200 mg, 0.43 mmol), 5-methyl-2-(methyloxy)-4-{1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}aniline (Example 163, step D) (127 mg, 0.39 mmol), and p-toluenesulfonic acid (197 mg, 1 mmol) were weighed into a 20 mL microwave vial. 7 mL of trifluoroethanol was added and the mixture was heated in the microwave to 150° C. for 1 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2.5 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 2 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (135 mg, 0.17 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.22 (s, 1H), 9.41 (d, J=6.04 Hz, 1H), 8.47 (s, 1H), 8.32 (s, 1H), 8.24 (d, J=5.31 Hz, 1H), 8.04 (d, J=7.69 Hz, 1H), 7.80 (d, J=7.87 Hz, 1H), 7.72 (d, J=8.97 Hz, 1H), 7.59 (t, J=7.69 Hz, 1H), 7.53 (s, 1H), 7.43-7.49 (m, 1H), 7.39 (t, J=8.06 Hz, 1H), 7.19 (t, J=8.06 Hz, 2H), 6.98 (t, J=6.87 Hz, 1H), 6.88 (s, 1H), 6.51 (d, J=5.13 Hz, 1H), 3.80 (s, 3H), 3.27-3.30 (m, 2H), 3.05 (s, 3H), 2.98-3.03 (m, 2H), 2.73 (t, J=6.87 Hz, 2H), 2.59-2.68 (m, 1H), 2.18 (s, 3H), 2.03-2.14 (m, 2H), 1.64-1.74 (m, 4H). MS (ESI): 752 [M+H]+.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)=[O:3].[NH2:15][C:16]1[CH:24]=[C:23]2[C:19]([CH:20]([CH2:41][Cl:42])[CH2:21][N:22]2[C:25](=[O:40])/[CH:26]=[CH:27]/[C:28]2[N:29]([CH3:39])[CH:30]=[C:31]([NH:33][C:34](=[O:38])[CH2:35][CH2:36][CH3:37])[CH:32]=2)=[CH:18][CH:17]=1.O>N1C=CC=CC=1>[C:34]([NH:33][C:31]1[CH:32]=[C:28](/[CH:27]=[CH:26]/[C:25]([N:22]2[C:23]3[C:19](=[CH:18][CH:17]=[C:16]([NH:15][C:2]([O:4][CH2:5][C:6]4[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=4)=[O:3])[CH:24]=3)[CH:20]([CH2:41][Cl:42])[CH2:21]2)=[O:40])[N:29]([CH3:39])[CH:30]=1)(=[O:38])[CH2:35][CH2:36][CH3:37]
Reactant: CCCC(=O)Nc1cc(/C=C/C(=O)N2CC(CCl)c3ccc(N)cc32)n(C)c1
Reactant: O=C(Cl)OCc1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Solvent: O
Product: CCCC(=O)Nc1cc(/C=C/C(=O)N2CC(CCl)c3ccc(NC(=O)OCc4ccc([N+](=O)[O-])cc4)cc32)n(C)c1
Temperature: 20 °C
Yield: 70.4 %

Procedure:
4-Nitrobenzyl chloroformate (52 mg, 0.24 mmol) was added to a solution of 8 (48 mg, 0.12 mmol) in dry pyridine (6 mL) and the yellow solution was stirred at 20° C. More 4-nitrobenzyl chloroformate (52 mg, 0.24 mmol) was added after 30 min. After a further 1 h water was added and the mixture stirred for 30 min until the oil that separated had solidified. The solid was filtered off, washed with water, dried, and triturated with hot EtOAc to give 1-[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-(chloromethyl)-6-[(4-nitrobenzyloxy)carbonyl]aminoindoline (8a) (49 mg, 71%) as a yellow solid, mp 207-209.5° C. 1H NMR [(CD3)2SO] δ6 9.91 (s, 1 H, NH), 9.76 (s, 1 H, NH), 8.40 (s, 1 H, H-7), 8.27 (d, J=8.7 Hz, 2 H, ArHo to NO2), 7.70 (d, J=8.7 Hz, 2 H, ArHm to NO2), 7.54 (d, J=15.0 Hz, 1 H. H-β) 7.28 (d, J=8.2 Hz, 1 H, H-4), 7.22 (d, J=1.5 Hz, 1 H, H-5′), 7.16 (d, J=8.2 Hz, 1 H, H-6), 6.71 (d, J=1.4 Hz, 1 H. H-3′), 6.64 (d, J=15.0 Hz, 1 H, H-α), 5.30 (s, 2 H, ArCH2O), 4.48-4.39 (m, 1 H, H-2), 4.12 (dd, J=10.5, 4.1 Hz, 1 H, ArCH2O), 4.48-4.39 (m, 1 H, H-2), 4.12 (dd, J=10.5, 4.1 Hz, 1 H, H-2), 3.98-3.92 (m, 1 H, CHCH2Cl), 3.85-3.76 (m, 2 H, CHCH2Cl), 3.68 (s, 3H, NCH3), 2.20 (t, J=7.3 Hz, 2 H, CH2CH2CH3), 1.58 (sx, J=7.4 Hz, 2 H, CH2CH2CH3), 0.89 (t, J=7.4 Hz, 3 H, CH2CH2CH3).
Reaction SMILES: C([N:4]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:19][C:20]3[C:28]([F:29])=[CH:27][C:26]([F:30])=[C:25]([NH2:31])[C:21]=3[C:22](=[O:24])[CH:23]=2)=[CH:14][C:13]=1[F:32])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]Br)(=O)C.[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.O>O1CCCC1>[NH2:31][C:25]1[C:21]2[C:22](=[O:24])[CH:23]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([NH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)=[C:13]([F:32])[CH:14]=3)[O:19][C:20]=2[C:28]([F:29])=[CH:27][C:26]=1[F:30]
Reactant: C1CCNC1
Reactant: CC(=O)N(CCCCCCBr)c1ccc(-c2cc(=O)c3c(N)c(F)cc(F)c3o2)cc1F
Solvent: O
Solvent: C1CCOC1
Product: Nc1c(F)cc(F)c2oc(-c3ccc(NCCCCCCN4CCCC4)c(F)c3)cc(=O)c12

Procedure:
500 mg (1.07 mmol) of 5-amino-2-[4-(6-bromohexylamino)-3-fluorophenyl]-6,8-difluoro-4H-1-benzopyran-4-one obtained in Example 52 was dissolved in 15 ml of tetrahydrofuran, 0.891 ml of pyrrolidine was added and the mixture was heated at reflux for 1.5 hours. Water was added to the reaction solution and the mixture was extracted with a mixed solvent of chloroform and methanol. The organic layer was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol:triethylamine=90:10:1) and recrystallized from chloroform/n-hexane to give Compound 54 which was converted into hydrochloride according to the same manner as that in Example 16 to give 88 mg (17%).
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3](N)=O.F[B-](F)(F)F.C([O+](CC)CC)C.[F:19][CH2:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([NH:27][C:28]2[C:33]([NH2:34])=[CH:32][N:31]=[C:30]3[CH:35]=[CH:36][S:37][C:29]=23)[CH2:23][CH2:22]1>O1CCCC1.C(O)C>[F:19][CH2:20][C@H:21]1[CH2:22][CH2:23][C@H:24]([N:27]2[C:28]3=[C:29]4[S:37][CH:36]=[CH:35][C:30]4=[N:31][CH:32]=[C:33]3[N:34]=[C:3]2[C@H:2]([OH:1])[CH3:6])[CH2:25][CH2:26]1
Reactant: Nc1cnc2ccsc2c1N[C@H]1CC[C@H](CF)CC1
Reactant: C[C@@H](O)C(N)=O
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@H](CF)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of (2R)-2-hydroxypropanamide (0.184 g, 2.07 mmol) and triethyloxonium tetrafluoroborate (0.371 g, 1.95 mmol) in tetrahydrofuran (2.8 mL) was stirred at room temperature for 2 h. The solvent was removed and the residue dissolved in ethanol (1.2 mL) and added to a suspension of N7-[trans-4-(fluoromethyl)cyclohexyl]thieno[3,2-b]pyridine-6,7-diamine (0.18 g, 0.64 mmol) in ethanol (4.3 mL). The resulting mixture was stirred at 80° C. for 1 h. The solvent was removed and the residue was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (0.10 g, 50%). LCMS calculated for C17H21FN3OS (M+H)+: m/z=334.1. Found: 334.1.
Reaction SMILES: [C:1]([OH:12])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]C.[C:13](O)(=[O:25])[CH2:14]CCCCCCCCCC.C(O)(=O)CCCCCCCCCCCCC.C(O)CO>ClCCl.OS(O)(=O)=O>[C:1]([O:12][CH2:14][CH2:13][OH:25])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCCCC(=O)O
Reactant: CCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCC(=O)O
Agent: O=S(=O)(O)O
Solvent: OCCO
Solvent: ClCCl
Product: CCCCCCCCC(=O)OCCO
Reaction time: 216 h

Procedure:
Decanoic acid (C10 acid), dodecanoic acid (C12 acid), and tetradecanoic acid (C14 acid)-each of 100 mmol of C10, C12 and C14 acids were dissolved in 50 ml dichloromethane, and 300 mmol of ethylene glycol was added to the solutions. Several drops of H2SO4 were added to the mixture. The reaction mixtures were stored at room temperature for 9 days. Isolation of the esters were carried out using the same procedure as that to isolate ethylene glycol monopelargonate. Distillations were not undertaken.
Reaction SMILES: ICI.[CH2:4]([Zn]CC)C.[CH3:9][O:10][CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]=[C:20]([CH3:22])[CH3:21])=[N:17][CH:18]=1>C1(C)C=CC=CC=1>[CH3:21][C:20]1([CH3:4])[CH2:22][CH:19]1[C:16]1[CH:15]=[CH:14][C:13]([O:12][CH2:11][O:10][CH3:9])=[CH:18][N:17]=1
Reactant: CC[Zn]CC
Reactant: COCOc1ccc(C=C(C)C)nc1
Solvent: ICI
Solvent: Cc1ccccc1
Product: COCOc1ccc(C2CC2(C)C)nc1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
Diiodomethane (24.8 ml, 308 mmol) was added dropwise to a solution of diethylzinc (200 ml, 220 mmol) 1.1 M in toluene at 0° C. After the addition, the solution was stirred at RT for 40 minutes and then recooled to 0° C. when 5-(methoxymethoxy)-2-(2-methylprop-1-enyl)pyridine (21.3 g, 110 mmol) in toluene (150 mL) was added dropwise through an addition funnel. The reaction was allowed to come to RT and was stirred 12 hrs before being quenched at 0° C. by the addition of a 10:1 saturated ammonium chloride/ammonium hydroxide aqueous solution. The layers were separated and the aqueous layer was diluted with water and extracted into ethyl acetate. The combined organic layers were washed with 10:1 saturated ammonium chloride/ammonium hydroxide aqueous solution, water, brine, dried over sodium sulfate, and concentrated. The crude product was purified through a plug of silica (10:1 Hexanes/EtOAc) to afford the titled compound. MS m/z: 208.2 (100%, M+1).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:9])=[C:4](N)[CH:5]=[CH:6][CH:7]=1.N([O-])=[O:11].[Na+]>S(=O)(=O)(O)O.O>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([OH:11])[CH:5]=[CH:6][CH:7]=1
Reactant: O=N[O-]
Reactant: Cc1c(N)cccc1Br
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Cc1c(O)cccc1Br
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
20 g (107 mmol) of 3-bromo-2-methylphenylamine are dissolved in 150 mL of aqueous 1.0M sulphuric acid and the mixture is cooled to 0° C. A solution of 8.9 g (129 mmol) of sodium nitrite in 20 mL of water is added slowly. The medium is stirred for 15 minutes at 0° C., and 50 mL of concentrated sulphuric acid are then added. The reaction medium is then heated at 100° C. for 1 hour and then cooled and diluted in water. After extraction with ethyl ether, the residue obtained is recrystallized from a heptane/dichloromethane mixture. A yellow solid is obtained (m.p.=89° C.; m=12.3 g; Y=61%).
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([CH:7]=[C:8]([C:18]#[N:19])[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:3][CH:2]=1.[Br:21]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:21][CH2:20][C:1]1[CH:2]=[CH:3][C:4]([CH:7]=[C:8]([C:18]#[N:19])[S:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[CH:5][CH:6]=1
Reactant: Cc1ccc(C=C(C#N)S(=O)(=O)c2ccccc2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: N#CC(=Cc1ccc(CBr)cc1)S(=O)(=O)c1ccccc1
Reaction time: 5 h

Procedure:
56.8 g (0.2 mole) of 1-p-tolyl-2-cyano-2-phenylsulfonylethylene were dissolved in 1.000 ml of anhydrous carbon tetrachloride at 40° to 50° C. After addition of 35.6 g (0.2 mole) of N-bromosuccinimide and 1.2 g of dibenzoylperoxide, the whole was heated to the boil under reflux. After 5 hours, the mixture was filtered by still hot; as residue 17.2 g (about 86%) of succinimide melting at 125° C remained behind. The filtrate was evaporated on a rotary steamer and under the vacuum produced by a water jet and the residue was recrystallized from 400 ml of ethanol. 47.4 g (65 of the theory) of weakly yellow crystal melting at 120° to 122° C were isolated. Characteristical NMR-signal in CDCl3 /TMS: --CH2Br at δ = 4.6 ppm. ##STR15##
Reaction SMILES: [Si]([O:8][CH2:9][C@@H:10]1[C@H:14]2[O:15][C:16]([CH3:19])([CH3:18])[O:17][C@H:13]2[C@H:12]([NH:20][C:21]2[CH:26]=[C:25]([C:27]#[C:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:24]=[CH:23][N:22]=2)[CH2:11]1)(C(C)(C)C)(C)C.F.N1C=CC=CC=1>C1COCC1.N1C=CC=CC=1>[CH3:18][C:16]1([CH3:19])[O:17][C@H:13]2[C@H:12]([NH:20][C:21]3[CH:26]=[C:25]([C:27]#[C:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[N:24]=[CH:23][N:22]=3)[CH2:11][C@H:10]([CH2:9][OH:8])[C@H:14]2[O:15]1
Reactant: CC1(C)O[C@@H]2[C@@H](CO[Si](C)(C)C(C)(C)C)C[C@@H](Nc3cc(C#Cc4ccccc4)ncn3)[C@@H]2O1
Agent: F
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CC1(C)O[C@@H]2[C@@H](CO)C[C@@H](Nc3cc(C#Cc4ccccc4)ncn3)[C@@H]2O1
Reaction time: 1.5 h
Yield: 82.1 %

Procedure:
To a solution of N-[(3aS,4R,6R,6aR)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-6-(phenylethynyl)pyrimidin-4-amine (0.275 g, 0.573 mmol) in THF (2 mL) and pyridine (2 mL) in a teflon vial was added pyridine hydrofluoride (1.3 mL, 0.014 mol) dropwise. The reaction was stirred for 1.5 h then quenched using a saturated aqueous Na2CO3 solution (15 mL) and EtOAc. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (0 to 5% MeOH/EtOAc) to afford the title compound as a yellow solid (0.172 g, 82%). LC/MS: Rt=1.29 min, ES+ 366 (FA standard).
Reaction SMILES: [Mn]([O-])(=O)(=O)=O.[K+].N1C=CC=CC=1.[C:13]([C:21]1[CH:22]=[CH:23]C(C)=[C:25]([N:27]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[C:28](=[O:30])[CH3:29])[CH:26]=1)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.[C:40]([O:43]CC)(=[O:42])[CH3:41]>O>[C:13]([C:21]1[CH:22]=[CH:23][C:41]([C:40]([OH:43])=[O:42])=[C:25]([N:27]([C:31]2[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=2)[C:28](=[O:30])[CH3:29])[CH:26]=1)(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCOC(C)=O
Reactant: CC(=O)N(c1ccc(F)cc1)c1cc(C(=O)c2ccccc2)ccc1C
Agent: O=[Mn](=O)(=O)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)N(c1ccc(F)cc1)c1cc(C(=O)c2ccccc2)ccc1C(=O)O
Temperature: 25 °C

Procedure:
Potassium permanganate 0.24 g was added to a mixed solution of pyridine 5.0 mL and water 5.0 mL of N-(5-benzoyl-2-methylphenyl)-N-(4-fluorophenyl)acetamide 0.52 g at room temperature, and it was heated and refluxed for 30 minutes. After the reaction mixture was cooled to room temperature, potassium permanganate 0.24 g was added to it, it was heated and refluxed for 30 minutes. After the reaction mixture was cooled to room temperature, potassium permanganate 0.24 g was added to it, it was heated and refluxed for 30 minutes. After the reaction mixture was cooled to room temperature, furthermore, potassium permanganate 0.24 g was added to it, and it was heated and refluxed for 30 minutes. After the reaction mixture was cooled, ethyl acetate was added to it, it was adjusted to pH2.3 with 6.0 mol/L hydrochloric acid, and insoluble matter was filtrated. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution, the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [eluent; hexane:ethyl acetate=1:2] to give 4-benzoyl-2-(N-(4-fluorophenyl)acetamido)benzoic acid 0.39 g of white solid.
Reaction SMILES: [H-].[Na+].[CH:3]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11])([CH3:5])[CH3:4].Br[CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=1.[Br-].[Na+]>COCCOC>[CH:3]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][O:11][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([S:24][CH3:25])=[CH:22][CH:23]=1)([CH3:5])[CH3:4]
Reactant: CSc1ccc(OCCCCBr)cc1
Reactant: CC(C)OCCCCO
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CSc1ccc(OCCCCOCCCCOC(C)C)cc1
Reaction time: 6 h

Procedure:
0.320 g (7.35 millimols) of 55% sodium hydride dispersion in oil are added by portions, over the course of 15 minutes and while stirring, to 1.02 g (7.7 millimols) of 4-isopropoxybutanol and 1.82 g (7.0 millimols) of 1-(4-bromo-butyloxy)-4-(methylthio)-benzene in 20 cc of absolute 1,2-dimethoxy ethane. The mixture is stirred at 20° for 18 hours and subsequently at 60° for 6 hours. The resulting sodium bromide is suction filtered, washed with ether and the filtrate is evaporated. After chromatography of the residue on silica gel with hexane/ethyl acetate (97:3) and (95:5), 1-[4-(4-isopropoxy-butyloxy)-butyloxy]-4-(methylthio)-benzene is obtained as a colourless oil.