Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]([CH3:5])=[CH2:4].C(=O)([O-])[O-].[K+].[K+].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]2[S:32][C:24]3[NH:25][C:26](=[O:31])[N:27]([CH3:30])[C:28](=[O:29])[C:23]=3[CH:22]=2)=[CH:16][CH:15]=1>CC(C)=O.[Cl-].[Na+]>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([CH2:20][C:21]2[S:32][C:24]3[N:25]([CH2:4][C:3]([CH3:5])=[CH2:2])[C:26](=[O:31])[N:27]([CH3:30])[C:28](=[O:29])[C:23]=3[CH:22]=2)=[CH:18][CH:19]=1
Reactant: C=C(C)CBr
Reactant: COc1ccc(Cc2cc3c(=O)n(C)c(=O)[nH]c3s2)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=C(C)Cn1c(=O)n(C)c(=O)c2cc(Cc3ccc(OC)cc3)sc21
Reaction time: 16 h

Procedure:
1-Bromo-2-methyl-2-propene (0.055ml) was added to a stirred suspension of potassium carbonate (0.203 g) and 6-(4-methoxyphenylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.15 g) in acetone (5 ml). After 16 h at room temperature, the mixture was diluted with saturated aqueous sodium chloride solution and extracted with ethyl acetate. The organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica, eluting with ethyl acetate:petroleum ether (1:3 then 3:7 then 7:13) to give the title compound (0.11 g).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:11]([O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(=O)c1ccccc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)c1ccccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
A mixture of 2′-hydroxyacetophenone (68.1 g, 0.500 mol), benzylbromide (94.1 g, 0.550 mol) and K2CO3 (103 g, 0.750 mol) in acetone (1.0 L) was heated at reflux, and the stirring was continued overnight. After cooled to room temperature, the mixture was concentrated under reduced pressure. The residue was diluted with water, and extracted with ethyl acetate. The separated organic phase was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by distillation under reduced pressure to give 1-[2-(benzyloxy)phenyl]ethanone as a colorless oil. (100 g, yield; 88%)
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([Cl:16])=[CH:9][CH:10]=3)[CH:5]([C:17](O)=[O:18])[C:4]=2[CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1.CO>CCOCC.O>[Cl:16][C:8]1[CH:9]=[CH:10][C:11]2[O:12][C:13]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:15][CH:14]=3)[CH:5]([CH2:17][OH:18])[C:6]=2[CH:7]=1
Reactant: O=C(O)C1c2cc(Cl)ccc2Oc2ccc(Cl)cc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: OCC1c2cc(Cl)ccc2Oc2ccc(Cl)cc21
Temperature: 25 °C
Yield: 53.6 %

Procedure:
A. From 2,7-Dichloroxanthene-9-carboxylic Acid: To a suspension of 0.75 g of LiAlH4 in 90 mL of anhydrous ether was added dropwise a solution of 3.0 g of 2,7-dichloroxanthene-9-carboxylic acid in 45 mL of freshly distilled THF over a period of 25 minutes. The mixture was stirred at room temperature until the color had changed from grey to light brown (ca. 6hr). The excess LiAlH4 was decomposed by the slow addition of 10 mL of methanol and 2 mL of water while stirring. The suspended precipitate was filtered, rinsed with ether (2×30 mL) and discarded. The combined filtrate was washed with water (2×40 mL), dried over MgSO4, and evaporated under reduced pressure to give 1.53 g (53.6%) of the alcohol as a white solid. Recrystallization from Skelly B--EtOAc (4:1) gave 1.21 g (42.36%) of the 2,7-dichloro-9-xanthenemethanol as a white fluffy solid, m.p. 134.5°-136° C.; IR (KBr): 3250 (b, OH) cm-1 ; 1H NMR (CDCl3): δ 1.65 (b, 1H, OH), 3.75 (d, 2H, CH2O), 4.01 (t, 1H, CH), 6.94-7.40 (m, 6H, aryl). Anal. Calcd for C14H10O2Cl2 : C, 59.81; H, 3.59. Found: C, 60.73; H, 3.91. B. From 9-Xanthenemethanol: To a suspension of 3.0 g of 9-xanthenemethanol and 4.2 g of N-chlorosuccinimide in 25 mL of freshly distilled THF and 12.5 mL of water was added dropwise 2.0 mL of conc. HCl over a period of 5 minutes. The mixture was stirred at room temperature for 6 hours and poured into 200 mL of water with stirring. The precipitated solid was filtered, rinsed with water (2×30 mL), and dried in air to afford 3.95 g (100%) of the crude alcohol. Recrystallization from Skelly B--EtOAc (4:1) gave 1.35 g (34%) of 2,7-dichloro-9-xanthenemethanol as a fluffy solid, m.p. 134.5°-136° C., identified by the mixture melting point, IR and NMR spectral comparison with an authentic sample obtained by the reduction of 2,7-dichloroxanthene-9-carboxylic acid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3]/[C:2]/1=[N:7]/[NH:8][C:9](=O)[C:10]([F:13])([F:12])[F:11].[ClH:15].C(OC)(C)(C)C>CO>[ClH:15].[F:11][C:10]([F:13])([F:12])[C:9]1[N:1]2[CH2:6][CH2:5][NH:4][CH2:3][C:2]2=[N:7][N:8]=1
Reactant: O=C(N/N=C1/CNCCN1)C(F)(F)F
Agent: Cl
Solvent: CO
Solvent: COC(C)(C)C
Product: FC(F)(F)c1nnc2n1CCNC2
Temperature: 55 °C
Yield: 90.7 %

Procedure:
A suspension of N′-((Z)-piperazin-2-ylidene)-trifluoroacetohydrazide (41 g) in methanol (170 mL) is stirred and heated to about 55° C. Hydrogen chloride (21 mL) is added to the reaction mixture and stirred for about 2 hours. The solution is cooled to 20° C. and methyl tert-butyl ether (423 mL) is added to it. The solution is further cooled to 0° C. and stirred for about 1 hour. The solid is filtered, washed with mixture of ethanol and methyl tert-butyl ether (82 mL) and dried at about 45° C. to afford the title compound. (Yield: 90.7%)
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([NH2:14])=[CH:11][CH:12]=2)[C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH3:15])[CH2:6][C:5]1([CH3:23])[CH3:22])(=[O:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:32]=[C:33]([O:37][CH3:38])[C:34]=1[O:35][CH3:36])[C:29](Cl)=[O:30].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:29](=[O:30])[C:28]3[CH:27]=[C:26]([O:25][CH3:24])[C:34]([O:35][CH3:36])=[C:33]([O:37][CH3:38])[CH:32]=3)=[CH:11][CH:12]=2)[C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH3:15])[CH2:6][C:5]1([CH3:23])[CH3:22])(=[O:3])[CH3:2]
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Reactant: CC(=O)N1c2ccc(N)cc2C(C)(c2ccccc2)CC1(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COc1cc(C(=O)Nc2ccc3c(c2)C(C)(c2ccccc2)CC(C)(C)N3C(C)=O)cc(OC)c1OC

Procedure:
Acylation of 1-acetyl-6-amino-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline (10 mg) with 3,4,5-trimethoxybenzoyl chloride (12 mg) and N,N-diisopropylethylamine (22 μl) in tetrahydrofuran (1 ml) was performed according to the method described in example 6.
Reaction SMILES: C(=O)([O-])[O-:2].[K+].[K+].[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[O:18][N:17]=[C:16]([O:19][CH2:20][CH:21]3[O:23][CH2:22]3)[CH:15]=2)[CH:11]=[CH:12][CH:13]=1.[Cl-].[Na+]>C(#N)C>[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[O:18][N:17]=[C:16]([O:19][CH2:20][CH:21]([OH:23])[CH2:22][OH:2])[CH:15]=2)[CH:11]=[CH:12][CH:13]=1
Reactant: O=C([O-])[O-]
Reactant: Clc1cccc(-c2cc(OCC3CO3)no2)c1
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Product: OCC(O)COc1cc(-c2cccc(Cl)c2)on1
Yield: 82.5 %

Procedure:
100 ml (72.3 mmoles) of a 10% w/v aqueous solution of potassium carbonate were added to a solution of 15.0 g (59.6 mmoles) of 5-(m-chlorophenyl)-3-(2,3-epoxypropoxy)isoxazole (prepared as described in Preparation 2) in 50 ml of acetonitrile, and the mixture was heated under reflux for 3 hours. At the end of this time, the reaction mixture was cooled by allowing it to stand, and then 400 ml of a 10% w/v aqueous solution of sodium chloride were added thereto, and the mixture was extracted twice, each time with 400 ml of ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was then purified by column chromatography through silica gel, eluted with a 1:2 by volume mixture of benzene and ethyl acetate, to give 13.2 g (yield 82.5%) of the title compound as a colorless amorphous powder, melting at 92°-93° C.
Reaction SMILES: [CH2:1]1[CH:6]2[NH:7][C:8](C[N:5]2[C:3](=[O:4])[CH2:2]1)=[O:9].C(OC1NC(=O)CC1)C.C(=O)([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)N.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH2:23]([O:22][C:8]([NH:7][CH:6]1[NH:5][C:3](=[O:4])[CH2:2][CH2:1]1)=[O:9])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C1CN2C(=O)CCC2N1
Reactant: NC(=O)OCc1ccccc1
Agent: CCOC1CCC(=O)N1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: O=C1CCC(NC(=O)OCc2ccccc2)N1

Procedure:
WO 93/09120 describes a process for the preparation of dimiracetam (2,5-dioxohexa-hydro-1H-pyrrolo[1,2-a]imidazole) 1 and related compounds. 5-Ethoxy-2-pyrrolidone is reacted with benzyl carbamate with a catalytic amount of p-toluenesulfonic acid to give 5-benzyloxycarbonylamino-2-pyrrolidone. This compound is then deprotonated at the pyrrolidine nitrogen with sodium hydride in acetonitrile, and reacted with ethyl bromoacetate to give ethyl 5-benzyloxycarbonylamino-2-oxo-1-pyrrolidine-acetate 2. Cyclization can then be performed after cleavage of the ethyl ester and/or the benzyloxycarbonyl protecting group in the presence of a variety of cyclizing agents.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]([CH3:13])[C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[NH2:8].[C:14]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1)([CH3:17])([CH3:16])[CH3:15].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C.O>[C:14]([C:18]1[CH:19]=[CH:20][C:21]([CH2:22][NH:23][C:10](=[O:12])[CH:9]([C:4]2[CH:5]=[CH:6][C:7]([NH2:8])=[C:2]([NH2:1])[CH:3]=2)[CH3:13])=[CH:24][CH:25]=1)([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C(=O)O)c1ccc(N)c(N)c1
Reactant: CC(C)(C)c1ccc(CN)cc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: O
Product: CC(C(=O)NCc1ccc(C(C)(C)C)cc1)c1ccc(N)c(N)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2-(3,4-Diaminophenyl)propanoic acid (436 mg, 2.42 mmol) in DMF (5 mL) was added 4-t-butylbenzylamine (399 mg, 2.44 mmol), EDC (702 mg, 3.66 mmol), HOBt (496 mg, 3.67 mmol), triethylamine (617 mg, 6.10 mmol) at 0° C. The reaction mixture was stirred for 16 hours at room temperature, and then the mixture was added water (50 mL) and extracted with methylene chloride. The organic layer was dried with MgSO4 and filtered. Methylene chloride was removed by evaporation. The residue was purified by column chromatography eluting with CH2Cl2/MeOH=20/1.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[Na+].C1COCC1.Cl[CH:17]([F:19])[F:18]>O>[F:18][CH:17]([F:19])[O:8][C:5]1[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=1
Reactant: FC(F)Cl
Reactant: Oc1ccc(I)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: FC(F)Oc1ccc(I)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
100 g (0.4.55 mol) of 4-iodophenol and 54.6 g (1.365 mol) of sodium hydroxide are added to a mixture of 300 ml of THF and 30 ml of water. After stirring for about 1/2 hour, the mixture is evaporated in a rotary evaporator; this is repeated after the addition of 200 ml of toluene. The residue is taken up in 400 ml of THF. The mixture is cooled to 0° C., 47.1 g (0.545 mol) of chlorodifluoromethane are introduced, and the mixture is then stirred for 1 hour. It is then stirred at about +5° C. for 18 hours. The solution above the resulting slurry-like precipitate was decanted off. It was evaporated in a rotary evaporator, and the residue was chromatographed through a silica gel column, using petroleum ether as eluent.
Reaction SMILES: [CH2:1]([C:4]1[N:5]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH2:24])=[O:23])[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].C1C=C(Cl)C=C(C(OO)=O)C=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[OH-].[NH4+:48]>>[NH2:48][C:8]1[C:7]2[N:16]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH2:24])=[O:23])[C:6]=2[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=1
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCCCC(N)=O
Reactant: [NH4+]
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [OH-]
Product: CCCc1nc2c(N)nc3ccccc3c2n1CCCCCC(N)=O

Procedure:
6-(2-Propyl-1H-imidazo[4,5-c]quinolin-1-yl)hexanamide (1.7 g, 5.2 mmol) was treated with mCPBA (3.61 g, 15.7 mmol) followed by ammonium hydroxide (40 mL) and p-toluenesulfonyl chloride (1.49 g, 7.84 mmol) according to the method described in Part D of Example 8. The crude product was purified as described in Part D of Example 8 to provide 0.137 g of 6-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)hexanamide as tan needles, mp 210-211° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](=[O:23])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18](Br)[CH:17]=1.[O:25]1[CH:29]=[CH:28][CH:27]=[C:26]1B(O)O>>[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](=[O:23])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:26]2[O:25][CH:29]=[CH:28][CH:27]=2)[CH:17]=1
Reactant: COC(=O)Cc1c(C(=O)c2cccc(Br)c2)[nH]c2cc(Cl)ccc12
Reactant: OB(O)c1ccco1
Product: COC(=O)Cc1c(C(=O)c2cccc(-c3ccco3)c2)[nH]c2cc(Cl)ccc12

Procedure:
The title compound was prepared according to the procedure described in Example 207 from methyl[6-chloro-2-(3-bromobenzoyl)-1H-indol-3-yl]acetate (Example 215) and furan-2-boronic acid.
Reaction SMILES: [CH:1]1([C:4]2[NH:12][C:11]3[C:10](=S)[NH:9][C:8](=[S:14])[N:7]([CH2:15][CH2:16][CH3:17])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[CH:18]1([NH2:23])[CH2:22][CH2:21][CH2:20][CH2:19]1.C1(C)CCC(C(C)C)C(O)C1.C(=O)(O)[O-]>>[CH:18]1([NH:23][C:10]2[C:11]3[NH:12][C:4]([CH:1]4[CH2:3][CH2:2]4)=[N:5][C:6]=3[N:7]([CH2:15][CH2:16][CH3:17])[C:8](=[S:14])[N:9]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: NC1CCCC1
Reactant: CCCn1c(=S)[nH]c(=S)c2[nH]c(C3CC3)nc21
Agent: CC1CCC(C(C)C)C(O)C1
Agent: O=C([O-])O
Product: CCCn1c(=S)nc(NC2CCCC2)c2[nH]c(C3CC3)nc21

Procedure:
5.33 g (20 mmoles) of 8-cyclopropyl-3-n-propyl-2,6-dithioxantine and 42 ml of cyclopentylamine were heated in a 450 ml pressure reactor to 150° C. (50 psi) with the exclusion of air. After 20 hours the solution was transferred with menthol to a round bottom flask and evaporated in vacuo to dryness. The residue is treated with 60 ml of water and 5N HCl to obtain a pH of 2. The suspension is neutralized with bicarbonate to pH 7, the solid collected, washed, dried, suspended in refluxing acetone and collected again: 5.98 g of thioisoguanine with mp 274-6° C. (decomp).
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[O:11][C:12]([C:18]([F:21])([F:20])[F:19])=[C:13]([C:15]([OH:17])=O)[N:14]=1.[CH3:24][O:25][CH2:26][CH2:27][N:28]([CH3:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][N:30]=1>>[CH3:24][O:25][CH2:26][CH2:27][N:28]([CH3:36])[C:29]1[N:30]=[CH:31][C:32]([NH:35][C:15]([C:13]2[N:14]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[O:3][C:2]([F:23])([F:22])[F:1])[O:11][C:12]=2[C:18]([F:21])([F:20])[F:19])=[O:17])=[CH:33][CH:34]=1
Reactant: COCCN(C)c1ccc(N)cn1
Reactant: O=C(O)c1nc(-c2ccccc2OC(F)(F)F)oc1C(F)(F)F
Product: COCCN(C)c1ccc(NC(=O)c2nc(-c3ccccc3OC(F)(F)F)oc2C(F)(F)F)cn1

Procedure:
With a procedure similar to example 16 above, 2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carboxylic acid {6-[(2-methoxy-ethyl)-methyl-amino]-pyridin-3-yl}-amide was prepared from 2-(2-trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carboxylic acid and N2-(2-methoxy-ethyl)-N2-methyl-pyridine-2,5-diamine. LCMS calcd for C21H18F6N4O4 (m/e) 504. obsd 505 (M+H).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][C:9]([C:12]1[CH:17]=[C:16]([SH:18])[CH:15]=[C:14]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:13]=1[OH:23])([CH3:11])[CH3:10].[CH:24]12[CH2:33][CH:28]3[CH2:29][CH:30]([CH2:32][CH:26]([CH2:27]3)[CH:25]1[NH:34][C:35](=[O:38])[CH:36]=[CH2:37])[CH2:31]2>CO>[CH3:11][C:9]([C:12]1[CH:17]=[C:16]([S:18][CH2:37][CH2:36][C:35]([NH:34][CH:25]2[CH:26]3[CH2:32][CH:30]4[CH2:29][CH:28]([CH2:33][CH:24]2[CH2:31]4)[CH2:27]3)=[O:38])[CH:15]=[C:14]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:13]=1[OH:23])([CH3:8])[CH3:10]
Reactant: C=CC(=O)NC1C2CC3CC(C2)CC1C3
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)(C)c1cc(SCCC(=O)NC2C3CC4CC(C3)CC2C4)cc(C(C)(C)C)c1O

Procedure:
Following the procedure of Example 4, triethylamine (0.5 ml) was added to a solution of 2,6-bis(1,1-dimethylethyl)-4-mercaptophenol (1.19 g, 0.005 mole) and the N-tricyclo[3.3.1.13,7 ]dec-2-yl-2-propenamide (1.02 g, 0.005 mole) in methanol (100 ml) and the solution stirred ar room temperature for 12 hours. The solvent and triethylamine were removed on a rotary evaporator and the product purified by chromatography on silica, recrystallized from ethyl acetate/ethyl ether/hexane and dried, m.p. ca. 155.5°-156° C. Analysis calc. for C27H41NO2S(443.69): Calc.: C, 73.09; H, 9.31; N, 3.16; S, 7.35. Found: C, 73.18; H, 9.23; N, 3.09; S, 7.21.
Reaction SMILES: [CH3:1][C:2]([CH3:4])=[O:3].[F:5][C:6]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:7]=1[CH:8]=O.[OH-].[Na+]>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.[Cl-].[Na+].O>[F:5][C:6]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:7]=1[CH:8]=[CH:1][C:2](=[O:3])[CH:4]=[CH:8][C:7]1[CH:10]=[CH:11][CH:12]=[C:13]([F:14])[C:6]=1[F:5]
Reactant: O=Cc1cccc(F)c1F
Reactant: CC(C)=O
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: O=C(C=Cc1cccc(F)c1F)C=Cc1cccc(F)c1F
Temperature: 25 °C
Reaction time: 48 h
Yield: 4.2 %

Procedure:
To a solution of 0.5 g (8.61 mmol) of acetone and 2.51 g (17.65 mmol) of 2,3-difluoro benzaldehyde in 86 mL of a 0.25M solution of aqueous NaOH (21.52 mmol) was added 1.13 mL (0.86 mmol) of a 25% w/w aqueous solution of cetyltrimethylammonium chloride. The mixture was allowed to stir vigorously at room temperature for 48 hours, at which point it was diluted with 100 ml of brine and extracted with two 75 mL portions of methylene chloride. The organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. The residue was recrystallized from ethyl acetate to provide 110 mg (4%) of a yellow powder.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[CH:9][NH:8][C:7]=12.[I:11]N1C(=O)CCC1=O>C(#N)C>[Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:10]([I:11])=[CH:9][NH:8][C:7]=12
Reactant: Clc1nccc2cc[nH]c12
Reactant: O=C1CCC(=O)N1I
Solvent: CC#N
Product: Clc1nccc2c(I)c[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.6 %

Procedure:
To a mixture of 7-chloro-1H-pyrrolo[2,3-c]pyridine (0.75 g, 4.92 mmol) and N-iodo-succinimide (1.2 g, 5.41 mmol) was added acetonitrile (31 mL) and the solution was heated to 75 C. After 1 h, the mixture was cooled to r.t., the formed solid was filtered, washed with acetonitrile, and dried to yield the title product (1.2 g). HRMS (ESI) calc (M+H)+=278.9180. found 278.9181.
Reaction SMILES: [CH3:1][C:2](C)([O-])C.[K+].[CH3:7][N:8]([CH3:23])[CH:9]=[CH:10][C:11]([C:13]1[CH:14]=[C:15]([NH:19][C:20](=[O:22])[CH3:21])[CH:16]=[CH:17][CH:18]=1)=[O:12].C(I)C.CCCCCC>CN(C)C=O.ClCCl>[CH3:23][N:8]([CH3:7])[CH:9]=[CH:10][C:11]([C:13]1[CH:14]=[C:15]([N:19]([CH2:1][CH3:2])[C:20](=[O:22])[CH3:21])[CH:16]=[CH:17][CH:18]=1)=[O:12]
Reactant: CC(=O)Nc1cccc(C(=O)C=CN(C)C)c1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCI
Product: CCN(C(C)=O)c1cccc(C(=O)C=CN(C)C)c1
Reaction time: 6 h

Procedure:
4.25 gm of Potassium tert-butoxide was added portion wise to a clear solution of 5 gm N-[3-[3-(Dimethylamino)-1-oxo-2-propenyl]-phenyl] acetamide in 50 ml dimethyl formamide. A solution of 5.25 gm Ethyl iodide in 20 ml dimethyl formamide was added drop wise over 3 hrs. at 35° C.-40° C. The reaction mass was stirred for 6 hrs and then quenched in 300 ml of water and extracted in dichloromethane. The organic layer was washed with water, dried over sodium sulphate and concentrated under vacuum to get oil, which was dissolved in 5 ml dichloromethane and 50 ml hexane was added to precipitate the product. The solids obtained was filtered and washed with hexane and dried in vacuum tray dryer at 35° C. for 6 hrs.
Reaction SMILES: [OH-].[K+].[CH2:3]([OH:6])[C:4]#[CH:5].[CH2:7](Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>Cl>[CH2:3]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:4]#[CH:5]
Reactant: ClCc1ccccc1
Reactant: C#CCO
Agent: Cl
Agent: [K+]
Agent: [OH-]
Product: C#CCOCc1ccccc1
Temperature: 25 °C
Yield: 69.6 %

Procedure:
Alternatively, solid potassium hydroxide (12.3 g, 0.22 mole) was stirred with propargyl alcohol (6.0 ml, 0.11 mole) and benzyl chloride (12.8 ml, 0.11 mole) at 60° C. for 16 hours. After cooling to 25° C., hydrochloric acid (80 ml, 3.0M aqueous solution) was added and extracted with hexanes (100 ml, 50 ml). The combined organic extracts were dried over magnesium sulfate and the solvent evaporated. The residue was distilled at 100 torr to afford propargylbenzyl ether as a colorless liquid (bp 140° C., 11.2 g, 71% yield).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH2:17][C@H:18]([N:20]([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH2:38][C:39]([F:42])([F:41])[F:40])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])[CH:7]=[C:8]2[C:12]=1[N:11]([CH2:13][CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]2)(=[O:3])[NH2:2].C([O-])=O.[NH4+]>CO.[Pd]>[C:1]([C:4]1[CH:5]=[C:6]([CH2:17][C@H:18]([N:20]([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH2:38][C:39]([F:40])([F:41])[F:42])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])[CH3:19])[CH:7]=[C:8]2[C:12]=1[N:11]([CH2:13][CH2:14][CH2:15][OH:16])[CH:10]=[CH:9]2)(=[O:3])[NH2:2]
Reactant: C[C@H](Cc1cc2c(c(C(N)=O)c1)N(CCCO)CC2)N(CCOc1ccccc1OCC(F)(F)F)C(=O)OC(C)(C)C
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: C[C@H](Cc1cc(C(N)=O)c2c(ccn2CCCO)c1)N(CCOc1ccccc1OCC(F)(F)F)C(=O)OC(C)(C)C
Yield: 102 %

Procedure:
tert-Butyl (R)-N-[2-[7-carbamoyl-1-(3-hydroxy-propyl)-2,3-dihydro-1H-indol-5-yl]-1-methylethyl]-N-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]carbamate (12.0 g) and ammonium formate (12.7 g) were dissolved in methanol (300 ml), and 10% palladium on carbon (1.20 g) was carefully added to the solution. The mixture was heated overnight under reflux, and the solvent was removed in vacuo. Water was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give amorphous tert-butyl (R)-N-[2-[7-carbamoyl-1-(3-hydroxy-propyl)-1H-indol-5-yl]-1-methylethyl]-N-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]carbamate (12.2 g).