Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+:2].[N:3]1([C:9]2[N:10]=[C:11]([CH2:16][C:17]([O:19]CC)=[O:18])[NH:12][C:13](=[O:15])[CH:14]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1>O1CCCC1>[N:3]1([C:9]2[N:10]=[C:11]([CH2:16][C:17]([O-:19])=[O:18])[NH:12][C:13](=[O:15])[CH:14]=2)[CH2:4][CH2:5][O:6][CH2:7][CH2:8]1.[Na+:2]
Reactant: CCOC(=O)Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
18.7 ml of 2M sodium hydroxide are added to a solution of 10 g of ethyl [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 300 ml of tetrahydrofuran. The reaction mixture is stirred for 48 hours at ambient temperature. The precipitate formed is filtered off through sintered glass, washed with ethyl acetate and rinsed several times with ethyl ether. The solid obtained is then dried in a rotary evaporator so as to give 8.7 g of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in the form of a white solid, the characteristics of which are the following:
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1.[F:16][C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1>CN(C=O)C>[F:16][C:17]1[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=1)[O:23][C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1
Reactant: Oc1cccc(F)c1
Reactant: N#Cc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: N#Cc1ccc(Oc2cccc(F)c2)cc1
Yield: 55.4 %

Procedure:
A DMF (83 mL) solution of K2CO3 (12.60 g, 91.3 mmol), 4-bromobenzonitrile (15.00 g, 83.0 mmol) and 3-fluorophenol (8.2 mL, 91.3 mmol) was stirred at reflux (24 h). DMF was removed by distillation and the residue was purified by flash column chromatography on silica gel with EtOAc/hexanes (0/10 to 5/95) as the eluent to obtain 4-((3′-fluoro)phenoxy)benzonitrile as a white solid (9.81 g, 56%): Rf=0.54 (EtOAc/hexanes 5/95); mp 67-69° C.; IR (nujol) 3073, 2961, 2912, 2862, 2219, 1593, 1461, 1376, 1265, 1225, 1163, 1119, 954, 869, 830, 788, 677, 543 cm−1; 1H NMR (300 MHz, CDCl3) δ 6.79 (dt, J=2.1, 9.9 Hz, 1 ArH), 6.84-6.98 (m, 2 ArH), 7.05 (d, J=9.0 Hz, 2H3), 7.32-7.41 (m, 1 ArH), 7.64 (d, J=9.0 Hz, 2H2); 13C NMR (75 MHz, CDCl3) δ 106.7 (C1), 107.9 (d, J=23.9 Hz, C2′ or C4′), 111.9 (d, J=21.1 Hz, C4′ or C2′), 115.6 (d, J=3.4 Hz, C6′), 118.5, 118.6 (CN, C3), 131.0 (d, J=9.7 Hz, C5′), 134.2 (C2), 156.2 (d, J=10.3 Hz, C1′), 160.7 (C4), 163.6 (d, J=247.1 Hz, C3′); HRMS (M+H+)(ESI+) not observed [M+H+] (calcd for C13H8FNOH+ 214.0668); Anal. Calcd. for C13H6FNO: C, 73.23; H, 3.78; F, 8.91; N, 6.57. Found: C, 73.18; H, 3.69; F, 8.68; N, 6.53.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[Si:9]([O:16][CH:17]([CH:39]=[CH2:40])[CH2:18][N:19]1[C:23]2[N:24]=[CH:25][N:26]=[C:27]([NH2:28])[C:22]=2[C:21]([C:29]2[CH:30]=[N:31][C:32]3[C:37]([CH:38]=2)=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:20]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].C(=O)(O)[O-].[Na+]>CN(C=O)C>[Br:1][C:20]1[N:19]([CH2:18][CH:17]([O:16][Si:9]([C:12]([CH3:13])([CH3:14])[CH3:15])([CH3:10])[CH3:11])[CH:39]=[CH2:40])[C:23]2[N:24]=[CH:25][N:26]=[C:27]([NH2:28])[C:22]=2[C:21]=1[C:29]1[CH:30]=[N:31][C:32]2[C:37]([CH:38]=1)=[CH:36][CH:35]=[CH:34][CH:33]=2
Reactant: C=CC(Cn1cc(-c2cnc3ccccc3c2)c2c(N)ncnc21)O[Si](C)(C)C(C)(C)C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CC(Cn1c(Br)c(-c2cnc3ccccc3c2)c2c(N)ncnc21)O[Si](C)(C)C(C)(C)C
Reaction time: 0.5 h
Yield: 90.1 %

Procedure:
N-Bromosuccinimide (894 mg) was added to a solution of 7-(2-(tert-butyldimethylsilyloxy)-3-butenyl)-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (2.13 g) obtained in Step 5 in DMF (25 ml) at room temperature. After stirring at the same temperature for 30 minutes, the mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a yellow solid (2.26 g).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22](O)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[O:23])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: C1CNCCN1
Reactant: O=C(O)C1(c2ccc(OCCCN3CCCC3)cc2)CCCCC1
Product: O=C(N1CCNCC1)C1(c2ccc(OCCCN3CCCC3)cc2)CCCCC1
Yield: 19 %

Procedure:
The title compound (351 mg, 19%) was prepared using 1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]cyclohexanecarboxylic acid and piperazine similarly to the procedure used for example 149. LRMS APCI+ m/z 400 [MH]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:13])[CH3:12])=[N:8][CH:9]=1)([O-])=O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[CH2:25]([N:32]1[C:36](=[O:37])[C:35](=[C:38]2[N:42]([CH3:43])[C:41]3[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=3[S:39]2)[S:34][CH2+:33]1SC)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH2:25]([N:32]1[C:36](=[O:37])[C:35](=[C:38]2[N:42]([CH3:43])[C:41]3[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=3[S:39]2)[S:34][C:33]1=[N:1][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:13])[CH3:12])=[N:8][CH:9]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CC(=O)Nc1ccc([N+](=O)[O-])cn1
Reactant: CS[CH2+]1SC(=C2Sc3ccccc3N2C)C(=O)N1Cc1ccccc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Product: CC(=O)Nc1ccc(N=C2SC(=C3Sc4ccccc4N3C)C(=O)N2Cc2ccccc2)cn1

Procedure:
In a manner similar to Example 30, intermediate N-(5-nitropyridin-2-yl)acetamide was hydrogenated and then condensed with 3-benzyl-5-(3-methyl-3H-benzothiazol-2-ylidene)-2-methylthio-4-oxo-2-thiazolium p-toluenesulfonate to afford the title compound. 1H-NMR (DMSO-d6): δ 10.45 (1H, s), 8.07 (1H, d), 7.97 (1H, d), 7.75 (1H, d), 7.33–7.46 (7H, m), 7.29 (1H, m), 7.22 (1H, m), 5.06 (2H, s), 3.79 (3H, s), 2.09 (3H, s); MS(ESI): 488 (MH+).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C@H:11]([C@@H:15]([NH:17][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH3:16])[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.[C:25](OC=O)(=[O:27])C>N1C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][C@H:11]([C@@H:15]([N:17]([CH:25]=[O:27])[O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH3:16])[C:12]([OH:14])=[O:13])=[CH:6][CH:7]=1
Reactant: CC(=O)OC=O
Reactant: Cc1ccc(CCC[C@@H](C(=O)O)[C@H](C)NOC2CCCCO2)cc1
Solvent: c1ccncc1
Product: Cc1ccc(CCC[C@@H](C(=O)O)[C@H](C)N(C=O)OC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 97 %

Procedure:
To a solution of (2R,3S)-2-(3-(4-methylphenyl)-1-propyl)-3-(2-tetrahydropyranyloxyamino)butanoic acid (114 mg, 0.34 mmol) in pyridine (2 mL) at 0° C. is added formic acetic anhydride (0.3 mL). The resulting solution is allowed to warm to 25° C., stirred for 3 h, and then concentrated to dryness under reduced pressure. The resulting gum is dissolved in ethyl acetate (30 mL) and washed sequentially with 1 M hydrochloric acid (20 mL) and saturated aqueous sodium chloride solution. The organic layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide (2R,3S)-2-(3-(4-methylphenyl)-1-propyl)-3-(formyl-2-tetrahydropyranyloxyamino)butanoic acid as an oil (120 mg, 97% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][OH:6].Br[CH2:12][C:13]1[CH:14]=[C:15]([CH2:21][CH:22]([O:26][CH:27]([CH3:29])[CH3:28])[C:23]([O-:25])=[O:24])[CH:16]=[CH:17][C:18]=1[O:19][CH3:20]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][O:6][CH2:12][C:13]1[CH:14]=[C:15]([CH2:21][CH:22]([O:26][CH:27]([CH3:29])[CH3:28])[C:23]([OH:25])=[O:24])[CH:16]=[CH:17][C:18]=1[O:19][CH3:20]
Reactant: OCc1ccc(Cl)c(Cl)c1
Reactant: COc1ccc(CC(OC(C)C)C(=O)[O-])cc1CBr
Product: COc1ccc(CC(OC(C)C)C(=O)O)cc1COCc1ccc(Cl)c(Cl)c1

Procedure:
Using 3,4-dichlorobenzyl alcohol and 3-[3-(bromomethyl)-4-methoxyphenyl]-2-isopropoxypropanoate, 3-(3-[(3,4-dichlorobenzyl)oxy]methyl-4-methoxyphenyl)-2-isopropoxypropanoic acid was obtained in the same method as in Example 247).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][CH:41]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:21]=[CH:22][C:23]([CH:26]5[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]5)=[N:24][CH:25]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[N:7]1>CO.Cl.O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][CH:41]=1)[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:25]=[N:24][C:23]([CH:26]5[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]5)=[CH:22][CH:21]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[N:7]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(-c3cnc4[nH]cc(-c5cnn(Cc6cccc(F)c6)c5)c4c3)cn2)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: Fc1cccc(Cn2cc(-c3c[nH]c4ncc(-c5ccc(C6CCNCC6)nc5)cc34)cn2)c1
Yield: 62.6 %

Procedure:
Using similar reaction conditions as described in step-ii of example-7, tert-butyl 4-(5-(3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridin-2-yl)piperidine-1-carboxylate (96 mg, 0.173 mmol) was deprotected in methanol/HCl in dioxane (5/5 ml) to afford 49 mg (63% yield) of the titled compound. 1H NMR (CD3OD, 300 MHz): δ 9.178-9.170 (d, 1H), 8.78-8.74 (dd, 1H), 8.71-8.66 (dd, 2H), 8.26 (s, 1H), 7.99 (s, 1H), 7.95-7.92 (d, 1H), 7.77 (s, 1H), 7.40-7.31 (q, 1H), 7.10-7.08 (d, 1H), 7.03-6.96 (m, 2H), 5.42 (s, 2H), 3.63-3.59 (d, 2H), 3.55-3.40 (m, 1H), 3.30-3.19 (m, 2H), 2.32-2.08 (m, 4H). MS: m/z=453.5 (M+1), HPLC: 93.40% in method A.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[CH3:19][N:20]1[CH:24]=[C:23]([S:25](Cl)(=[O:27])=[O:26])[N:22]=[C:21]1[CH3:29]>>[F:8][C:7]1[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])=[C:5]([NH:18][S:25]([C:23]2[N:22]=[C:21]([CH3:29])[N:20]([CH3:19])[CH:24]=2)(=[O:27])=[O:26])[CH:4]=[CH:3][C:2]=1[F:1]
Reactant: Cc1nc(S(=O)(=O)Cl)cn1C
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Product: Cc1nc(S(=O)(=O)Nc2ccc(F)c(F)c2Nc2ccc(I)cc2F)cn1C

Procedure:
According to the general procedure B, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene-1,2-diamine was reacted with 1,2-dimethyl-1H-imidazole-4-sulfonyl chloride to obtain the title compound. 1H NMR (300 MHz, CDCl3): δ 7.95 (br s, 1H), 7.37 (dd, J=1.8 & 10.8 Hz, 1H), 7.32-7.14 (m, 3H), 6.98 (dd, J=9.6 & 17.7 Hz, 1H), 5.87 (dt, J=4.2, 9.0 & 17.4 Hz, 1H), 5.55 (br s, 1H), 3.49 (s, 3H), 2.31 (s, 3H).
Reaction SMILES: C([O:5][C:6](=[O:35])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)[N:15]=1)([CH3:9])[CH3:8])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH2:28]([N:18]([C:19]1[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=1)[CH2:17][CH2:16][C:14]1[N:15]=[C:11]([S:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:35])=[O:5])[S:12][CH:13]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCN(CCc1csc(SC(C)(C)C(=O)OC(C)(C)C)n1)c1ccc([N+](=O)[O-])cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCCCCN(CCc1csc(SC(C)(C)C(=O)O)n1)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 60.5 %

Procedure:
2-[(4-{2-[Heptyl(4-nitrophenyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (200 mg) obtained in Example 303-3 was dissolved in dichloromethane (5 mL), trifluoroacetic acid (5 mL) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and hexane was added to the residue to give the title compound (108 mg) as a pale-yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].[Cl-].[Al+3].[Cl-].[Cl-].[Cl:14][CH2:15][C:16](Cl)=[O:17].Cl>C(=S)=S>[Cl:14][CH2:15][C:16]([C:7]1[CH:6]=[CH:5][C:4]([OH:9])=[C:3]([O:2][CH3:1])[CH:8]=1)=[O:17]
Reactant: COc1ccccc1O
Reactant: O=C(Cl)CCl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: COc1cc(C(=O)CCl)ccc1O
Temperature: 0 °C
Yield: 64 %

Procedure:
To a cooled (ice bath) stirred solution of 130.3 g (1.05 mole) of 2-methoxyphenol in 750 mL of carbon disulfide was continuously added 306.6 g (2.3 mole) of anhydrous aluminum chloride portionwise. The stirred, cooled mixture was then treated dropwise with 80 mL (113 g, 1.0 mole) of 2-chloroacetyl chloride. After the addition was completed, the mixture was heated at reflux temperature for 20 hr, cooled, and poured into a mixture of 2 kg of crushed ice and 200 ml of concentrated hydrochloric acid. The solid which gradually crystallized was washed with water and carbon disulfide and dried. The solid was recrystallized from isopropyl ether containing a few drops of 2-propanol to yield 128.3 g (64% yield) of the title compound, mp 102°-103° C.
Reaction SMILES: [N:1]1[N:9]2[C:4]([N:5]=[C:6]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:7]3=[C:8]2O)=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:18])=O.C(N(C(C)C)CC)(C)C>C1(C)C=CC=CC=1>[Cl:18][C:8]1[N:9]2[C:4]([N:5]=[C:6]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:7]=13)=[CH:3][CH:2]=[N:1]2
Reactant: Oc1c2c(nc3ccnn13)CCCCC2
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: Clc1c2c(nc3ccnn13)CCCCC2
Temperature: 25 °C
Yield: 35.3 %

Procedure:
To a suspension of 6,7,8,9-tetrahydro-5H-1,4,10a-triaza-cyclohepta[f]inden-10-ol (5 g, 29.4 mmol) in toluene (20 mL) was added phosphorus oxychloride (37 g, 246 mmol) and diisopropylethylamine (3.1 g, 24.6 mmol). The mixture was heated to reflux for 40 min then cooled to room temperature. The product crystallized from the reaction mixture on standing over a two-day period at room temperature. The solid was collected and washed with ether to give 10-chloro-6,7,8,9-tetrahydro-5H-1,4,10a-triaza-cyclohepta[f]indene (2.3 g, 42.5% yield). The product was used without further purification.
Reaction SMILES: [CH2:1]([C:12]1[N:16]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=2)[O:14][N:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:25][C:26]([NH2:38])([C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[CH3:27]>>[CH3:27][C:26]([NH:38][CH2:21][C:20]1[CH:23]=[CH:24][C:17]([C:15]2[O:14][N:13]=[C:12]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[N:16]=2)=[CH:18][CH:19]=1)([C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=1)[CH3:25]
Reactant: CC(C)(N)c1ccc(C(F)(F)F)cc1
Reactant: CCCCCCCCCCCc1noc(-c2ccc(C=O)cc2)n1
Product: CCCCCCCCCCCc1noc(-c2ccc(CNC(C)(C)c3ccc(C(F)(F)F)cc3)cc2)n1
Yield: 78 %

Procedure:
The same procedure as employed in the preparation of Example 226 (step a) but using 4-(3-undecyl-1,2,4-oxadiazol-5-yl)benzaldehyde and 1-methyl-1-[4-(trifluoromethyl)phenyl]ethylamine gave the title compound as a colorless oil (78%). 1H NMR (CDCl3, 300 MHz) δ 8.07 (d, J=7.9 Hz, 2H), 7.73-7.59 (m, 4H), 7.49 (d, J=8.3 Hz, 2H), 3.57 (s, 2H), 2.80 (t, J=7.5 Hz, 2H), 1.89-1.74 (m, 2H), 1.57 (s, 3H), 1.47-1.17 (m, 19H), 0.88 (t, J=7.0 Hz, 3H). M+(LC/MS(ESI)): 516.3. HPLC (Condition A), Rt: 5.02 min (HPLC purity: 98.2%).
Reaction SMILES: [C:1](Cl)(=[O:7])[CH2:2]CCCC.[C:9]1([C:15]#[C:16][C:17]2[CH:35]=[CH:34][C:20]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30](=[O:33])(=[O:32])[NH2:31])=[O:22])=[CH:19][CH:18]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CN(C)C1C=CN=CC=1.O1CCCC1>[C:9]1([C:15]#[C:16][C:17]2[CH:35]=[CH:34][C:20]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30]([NH:31][C:1](=[O:7])[CH3:2])(=[O:33])=[O:32])=[O:22])=[CH:19][CH:18]=2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CCCCCC(=O)Cl
Reactant: NS(=O)(=O)c1ccccc1NC(=O)c1ccc(C#Cc2ccccc2)cc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CC(=O)NS(=O)(=O)c1ccccc1NC(=O)c1ccc(C#Cc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.6 %

Procedure:
In a stream of nitrogen and at 0° C., 0.20 ml (1.46 mmol) of hexanoyl chloride was added to an anhydrous tetrahydrofuran (10 ml) solution containing 500 mg (1.30 mmol) of 4-phenylethynyl-N-(2-sulfamoylphenyl)benzamide produced in Reference Example 10 and 320 mg (2.60 mmol) of 4-dimethylaminopyridine, the mixture was stirred at room temperature for 1 hour and then the solvent was evaporated under a reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with water, a potassium hydrgensulfate aqueous solution and saturated brine in that order and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography to obtain 460 mg (yield: 74.6%) of the title compound.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[CH2:15][CH2:14][CH2:13][N:4]1[C@@H](C(Cl)(Cl)Cl)[O:6][C:7]2=O.[NH3:16].CO>>[OH:1][CH2:2][C@@:3]1([C:7]([NH2:16])=[O:6])[CH2:15][CH2:14][CH2:13][NH:4]1
Reactant: N
Reactant: O=C1O[C@H](C(Cl)(Cl)Cl)N2CCC[C@@]12CO
Solvent: CO
Product: NC(=O)[C@]1(CO)CCCN1
Temperature: 75 °C

Procedure:
(3R,7aR)-7a-Hydroxymethyl-3-trichloromethyl-tetrahydro-pyrrolo[1,2-c]oxazol-1-one (Stage J.1, 308 mg, 1.122 mmol) was added to 7 M ammonia in MeOH (8.014 mL, 56.1 mmol) under argon and heated at 75° C. in a sealed vessel for 72 h and then evaporated to give the title compound as a viscous pale brown oil which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1F)[C:5]#[N:6].C1(OC2C=CC=CC=2)C=CC=CC=1.[K].[CH3:26][O:27][C:28](=[O:39])[C:29]1[CH:34]=[C:33]([OH:35])[CH:32]=[CH:31][C:30]=1[N+:36]([O-:38])=[O:37]>CN1CCCC1=O>[CH3:26][O:27][C:28](=[O:39])[C:29]1[CH:34]=[C:33]([O:35][C:9]2[C:8]([F:11])=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[Cl:1])[CH:32]=[CH:31][C:30]=1[N+:36]([O-:38])=[O:37]
Reactant: COC(=O)c1cc(O)ccc1[N+](=O)[O-]
Reactant: N#Cc1cc(F)c(F)c(Cl)c1
Agent: [K]
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CN1CCCC1=O
Product: COC(=O)c1cc(Oc2c(F)cc(C#N)cc2Cl)ccc1[N+](=O)[O-]

Procedure:
The product 3-chloro-4,5-difluorobenzonitrile, prepared for example as set forth in Example 3, above, is a useful intermediate for the preparation of various end products especially for the preparation of diphenyl ether herbicides. Thus, for example, this compound may be further reacted with the potassium salt of methyl-5-hydroxy-2-nitrobenzoate in a solvent, such as N-methyl-2-pyrrolidone at a temperature of about 120° to 180° Celsius to form methyl-5-(2-chloro-4-cyano-6-fluoro-phenoxy)-2-nitro-benzoate. The ester may be hydrolyzed in a conventional manner to the corresponding carboxylic acid.
Reaction SMILES: [Br:1]Br.C([O-])(O)=O.[Na+].[CH3:8][CH:9]([CH3:15])[CH:10]=[CH:11][C:12](=[O:14])[CH3:13]>C(Cl)(Cl)(Cl)Cl>[Br:1][C:11](=[CH:10][CH:9]([CH3:15])[CH3:8])[C:12](=[O:14])[CH3:13]
Reactant: CC(=O)C=CC(C)C
Reactant: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: CC(=O)C(Br)=CC(C)C
Reaction time: 2 h
Yield: 43 %

Procedure:
A solution of 84 g of bromine in 75 ml of CCl4 was added dropwise to a mixture of 42 g of NaHCO3 and 56 g of 5-methyl-3-hexen-2-one in 175 ml of CCl4 at 0° C. while stirring in the course of 2 hours. The reaction mixture was stirred for a further hour at 0° C. and then filtered off and evaporated down. The residue was taken up in 150 ml of a 1:1 mixture of ethanol and water, to which 63 g of NaHCO3 had been added. The mixture was heated to reflux while stirring for 2 hours. After cooling, it was poured out into ice-water. This mixture was extracted three times with pentane. This extract was washed twice with water, dried over MgSO4, filtered off and evaporated down. The residue was distilled, 41 g of 3-bromo-5-methyl-3-hexen-2-one (E) being obtained, b.p. 62°-82° C./2 kPa.
Reaction SMILES: [H-].[Na+].Cl.[CH3:4][N:5]([CH2:7][CH2:8]Cl)[CH3:6].[CH2:10]([N:12]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[NH:16][C:15](=[O:23])[C:14]2=[CH:24][S:25][CH:26]=[C:13]12)[CH3:11]>CN(C)C=O>[CH3:4][N:5]([CH3:6])[CH2:7][CH2:8][N:16]1[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N:12]([CH2:10][CH3:11])[C:13]2=[CH:26][S:25][CH:24]=[C:14]2[C:15]1=[O:23]
Reactant: CN(C)CCCl
Reactant: CCN1c2ccccc2NC(=O)c2cscc21
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN1c2cscc2C(=O)N(CCN(C)C)c2ccccc21
Reaction time: 18 h

Procedure:
A mixture of 0.31 g. of 55% sodium hydride-mineral oil dispersion and 0.50 g. of dimethylaminoethylchloride hydrochloride in 25 ml. of dry dimethylformamide is stirred at room temperature for 0.5 hours. To the mixture is added 0.43 g. of 4,9-dihydro-4-ethyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one and stirring is continued for 18 hours. The reaction mixture is cooled, quenched with water, and extracted with chloroform. The dried chloroform extracts are concentrated to an oil, which is purified by preparative thin layer chromatography on silica gel with 10:1 benzene:methanol as eluent. The oily solid thus obtained is recrystallized from hexane to give white crystals, m.p. 75°-77° C.
Reaction SMILES: Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:10][C:5]2=[N:4][CH:3]=1.[F:15][C:16]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O>>[F:15][C:16]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:10][C:5]2=[N:4][CH:3]=1
Reactant: OB(O)c1cccc(-c2cccnc2)c1F
Reactant: CC(C)(O)c1ccn2c(Br)cnc2n1
Product: CC(C)(O)c1ccn2c(-c3cccc(-c4cccnc4)c3F)cnc2n1

Procedure:
2-(3-Bromoimidazo[1,2-α]pyrimidin-7-yl)propan-2-ol was coupled with 2-fluoro-3-(pyridin-3-yl)benzeneboronic acid as described in Example 1 to give 2-[3-(2-fluoro-3-(pyridin-3-yl)phenyl)imidazo[1,2-α]pyrimidin-7-yl]propan-2-ol as a white solid. Bis-hydrochloride salt (from ethyl acetate/ethanol): δH (360 MHz, DMSO) 1.56 (6H, s), 7.65 (1H, dd, J 8 and 8), 7.79-7.83 (1H, m), 7.85-7.87 (2H, m), 7.92-7.97 (1H, m), 8.48 (1H, d, J 7), 8.55 (1H, s), 8.83 (1H, dd, J 5 and 1), 9.10 (1H, s), 9.29 (1H, dd, J 7 and 3); m/z (ES+) 349 (M++H).
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2.[Cl:15][C:16]1[C:24]2[CH:23]=[C:22]([C:25]3[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=3)[S:21][C:20]=2[CH:19]=[CH:18][CH:17]=1.C(O)C.[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36]>C(OCC)(=O)C>[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36].[Cl:15][C:16]1[C:24]2[CH:23]=[C:22]([C:25]3[CH2:26][CH2:27][N:28]([CH2:3][C@H:2]([OH:1])[CH2:4][O:5][C:6]4[CH:14]=[CH:13][CH:12]=[C:11]5[C:7]=4[CH:8]=[CH:9][NH:10]5)[CH2:29][CH:30]=3)[S:21][C:20]=2[CH:19]=[CH:18][CH:17]=1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Reactant: Clc1cccc2sc(C3=CCNCC3)cc12
Agent: O=C(O)C(=O)O
Solvent: CCO
Solvent: CCOC(C)=O
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CC=C(c2cc3c(Cl)cccc3s2)CC1

Procedure:
The title compound was prepared in a fashion similar to that described in Example 1 using (S)-(+)-4-(oxiranylmethoxy)-1H-indole (0.129 g, 0.068 mmol) and 4-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl) benzo[b]thiophene (0.170 g, 0.068 mmol) using ethanol as reaction solvent. Yield 0.105 g (34%) of a tan powder. FDMS m/e=438 (M+ of free base). A sample was dissolved in ethyl acetate and treated with 1.0 equivalent of oxalic acid and evaporated to an orange powder. mp 138°-142° C. (dec) α[D]589 =-5.3 (c=1.13, dimethylsufoxide).