Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[S:5][C:6](Cl)=[CH:7][CH:8]=1)(=O)C.[Cl:10][C:11]1[S:15][C:14]([C:16]([CH2:18][C:19]#[N:20])=[O:17])=[CH:13][CH:12]=1.[CH2:21]([N:28]1CCC(=O)CC1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.N1CCOCC1.[S]>>[NH2:20][C:19]1[S:5][C:4]2[CH2:1][N:28]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:6][CH2:7][C:8]=2[C:18]=1[C:16]([C:14]1[S:15][C:11]([Cl:10])=[CH:12][CH:13]=1)=[O:17]
Reactant: CC(=O)c1ccc(Cl)s1
Reactant: N#CCC(=O)c1ccc(Cl)s1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: [S]
Solvent: C1COCCN1
Product: Nc1sc2c(c1C(=O)c1ccc(Cl)s1)CCN(Cc1ccccc1)C2
Yield: 63 %

Procedure:
The procedure of Example 1 was followed except that 2-acetyl-5-chlorothiophene (Aldrich) was used in place of acetophenone to prepare the corresponding 2-(5-chlorothiophene-2-carbonyl)acetonitrile (Steps A and B). 1-Benzyl-4-piperidone (van der Klein et al., (1999) J. Med. Chem. 42: 3629-3635), 2-(5-chlorothiophene-2-carbonyl)acetonitrile, morpholine, and sulfur were reacted according to the procedure of Step C, Example 1, to afford the desired compound. Yield: 63%; IR (KBr) cm−1: 3306, 2956, 2807, 1715, 1574, 1428, 1354, 1122, 1008, 742, 699; 1H NMR (CDCl3):δ2.39 (m, 2H), 2.59 (t, 2H, J=5.2 Hz), 3.45 (s, 2H), 3.67 (s, 2H), 6.26 (bs, 2H), 6.87 (d, 1H, J=3.8 Hz), 7.19 (d, 1H, J=4 Hz), 7.35 (m, 5H); yellow solid, mp: 81-83° C. (petroleum ether).
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([O:12][CH3:13])[C:6]2[O:10][CH2:9][O:8][C:7]=2[CH:11]=1.[C-:14]#[N:15].[Na+].O>CS(C)=O>[CH3:13][O:12][C:5]1[C:6]2[O:10][CH2:9][O:8][C:7]=2[CH:11]=[C:3]([CH2:2][C:14]#[N:15])[CH:4]=1
Reactant: COc1cc(CCl)cc2c1OCO2
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc(CC#N)cc2c1OCO2
Reaction time: 3 h
Yield: 60.2 %

Procedure:
To a solution of 6-(chloromethyl)-4-methoxybenzo[d][1,3]dioxole (10 g, 40 mmol) in DMSO (100 mL) was added NaCN (2.4 g, 50 mmol) at room temperature. The mixture was stirred for 3 h and poured into water (500 mL). The aqueous phase was extracted with EtOAc (100 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated to give the crude product, which was washed with ether to afford 2-(7-methoxybenzo[d][1,3]dioxol-5-yl)acetonitrile (4.6 g, 45%). 1H NMR (400 MHz, CDCl3) δ 6.49 (s, 2H), 5.98 (s, 2H), 3.91 (s, 3H), 3.65 (s, 2H). 13C NMR (400 MHz, CDCl3) δ 148.9, 143.4, 134.6, 123.4, 117.3, 107.2, 101.8, 101.3, 56.3, 23.1.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12])[CH3:3].[I:14][CH3:15]>C(Cl)Cl>[I-:14].[CH3:3][N+:2]([CH3:15])([CH3:1])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-:13])=[O:12]
Reactant: CN(C)Cc1ccccc1[N+](=O)[O-]
Reactant: CI
Solvent: ClCCl
Product: C[N+](C)(C)Cc1ccccc1[N+](=O)[O-]
Product: [I-]
Reaction time: 12 h
Yield: 167.6 %

Procedure:
The mixture of 57b (0.18 g, 0.5 mmol) and iodomethane (0.71 g, 5 mmol) in anhydrous CH2Cl2 (5 mL) was stirred for 12 h at r. t., then added additional iodomethane (0.71 g, 5 mmol) and continuously stirred for 12 h. After evaporation, the residue was dispensed with CH2Cl2 and filtered to give 58b (0.27 g, 84%) as yellow solid.
Reaction SMILES: CON(C)[C:4]([C:6]1[C:7]([NH2:15])=[N:8][C:9]([S:12][CH2:13][CH3:14])=[N:10][CH:11]=1)=[O:5].[C:17]1([CH3:25])[CH:22]=[CH:21][C:20]([Mg]Br)=[CH:19][CH:18]=1>O1CCCC1>[NH2:15][C:7]1[C:6]([C:4]([C:20]2[CH:21]=[CH:22][C:17]([CH3:25])=[CH:18][CH:19]=2)=[O:5])=[CH:11][N:10]=[C:9]([S:12][CH2:13][CH3:14])[N:8]=1
Reactant: Cc1ccc([Mg]Br)cc1
Reactant: CCSc1ncc(C(=O)N(C)OC)c(N)n1
Solvent: C1CCOC1
Product: CCSc1ncc(C(=O)c2ccc(C)cc2)c(N)n1
Reaction time: 2 h

Procedure:
To a solution of 4-amino-2-ethylsulfanyl-pyrimidine-5-carboxylic acid methoxy-methyl-amide (500 mg, 2.06 mmol, Example 1) in dry tetrahydrofuran (6 mL) at −30˜−40° C., was added 4-tolylmagnesium bromide (10.5 mL, Aldrich). The reaction was stirred at the same temperature for 2 hours before quenching with aqueous ammonium chloride. Work-up and purification as in Example 47 gave (4-amino-2-ethylsulfanyl-pyrimidin-5-yl)-p-tolyl-methanone as a white solid. MS (M+H)+, 274.
Reaction SMILES: O[C:2]1[CH:7]=[CH:6][C:5](CO)=[CH:4][N:3]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:11].[CH:16]([Cl:19])(Cl)Cl.O>P(Cl)(Cl)(Cl)=O>[Cl:11][C:2]1[CH:7]=[CH:6][C:5]([CH2:16][Cl:19])=[CH:4][N:3]=1
Reactant: ClC(Cl)Cl
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: OCc1ccc(O)nc1
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: ClCc1ccc(Cl)nc1
Yield: 95 %

Procedure:
A solution of 2.5 g (20 mmol) of 2-hydroxy-5-hydroxymethylpyridine and 4.16 g of phosphorus pentachloride in 10 ml of phosphoryl chloride was stirred for 6 hours at 105° C. After cooling, 50 ml of chloroform was added, the excess chlorination reagent being hydrolyzed by careful addition of water. The organic phase was washed with NaHCO3 solution, dried on NaSO4 and concentrated by evaporation. The distillation of the oily residue at 16 mm and 120° C. yielded 3.08 g of 2-chloro-5-chloromethyl-pyridine as a colorless oil that solidified during the cooling. The latter corresponds to a yield of 95 percent relative to the 2-hydroxy-5-hydroxymethyl-pyridine. Further data concerning the product was:
Reaction SMILES: [CH2:1]([NH:3][CH3:4])[CH3:2].Cl[CH2:6][CH2:7][CH2:8][OH:9].[I-].[Na+].O1CCOCC1>[OH-].[Na+]>[CH2:1]([N:3]([CH2:6][CH2:7][CH2:8][OH:9])[CH3:4])[CH3:2].[CH2:1]([N:3]([CH:7]([CH3:6])[CH2:8][OH:9])[CH3:4])[CH3:2]
Reactant: CCNC
Reactant: OCCCCl
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCN(C)C(C)CO
Product: CCN(C)CCCO
Temperature: 65 °C
Reaction time: 72 h
Yield: 63.5 %

Procedure:
3-(N-ethyl-N-methylamino)propanol was prepared as follows: In a pressure vessel was mixed N-ethyl-N-methylamine (25 g, 420 mmol), 3-chloropropanol (14.1 mL, 16 g, 170 mmol), sodium iodide (2.54 g, 17 mmol) and 60 mL dioxane. The vessel was sealed and heated to 65° C. After 3 days the reaction was allowed to cool to ambient temperature. Solvent was removed by rotary evaporation leaving a brown oil. The oil was dissolved in 80 mL of 2N NaOH, extracted with EtOAc (3×250 mL) and dried over Na2SO4. After filtration of the drying agent solvent was removed in vacuo leaving a brown oil. The oil was distilled (75° C., 15 mm Hg) leaving 2-(N-ethyl-N-methylamino)propanol (6.3 g, 54 mmol, 32% yield) as a colorless oil.
Reaction SMILES: [CH:1]1([CH2:4][N:5]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH2:6][C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.Cl[C:20]([O:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][N:31]=2)=[CH:25][CH:24]=1)=[O:21].C(NC(C)C)(C)C>CN(C)C=O>[F:38][C:36]([F:37])([F:39])[C:33]1[CH:34]=[CH:35][C:30]([O:29][C:26]2[CH:27]=[CH:28][C:23]([O:22][C:20]([N:16]3[CH2:15][CH2:14][CH:13]([N:5]([CH2:4][CH:1]4[CH2:2][CH2:3]4)[CH2:6][C:7]4[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=4)[CH2:18][CH2:17]3)=[O:21])=[CH:24][CH:25]=2)=[N:31][CH:32]=1
Reactant: c1cncc(CN(CC2CC2)C2CCNCC2)c1
Reactant: O=C(Cl)Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1
Solvent: CC(C)NC(C)C
Solvent: CN(C)C=O
Product: O=C(Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cc1)N1CCC(N(Cc2cccnc2)CC2CC2)CC1

Procedure:
The title product was prepared from cyclopropylmethyl-piperidin-4-yl-pyridin-3-ylmethylamine and 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent: dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (47%, off-white solid. HPLC-MS m/z=(M+1) 513.3, Rt: 2.70 min.
Reaction SMILES: Cl[C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16].[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Br:17][C:18]1[CH:19]=[C:20]([NH:21][C:2]2[C:11]3[CH:10]=[C:9]4[N:12]=[CH:13][N:14]=[C:8]4[CH2:7][C:6]=3[N:5]=[CH:4][C:3]=2[C:15]#[N:16])[CH:22]=[CH:23][CH:24]=1
Reactant: Nc1cccc(Br)c1
Reactant: N#Cc1cnc2c(c1Cl)C=C1N=CN=C1C2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCCO
Solvent: c1ccncc1
Product: N#Cc1cnc2c(c1Nc1cccc(Br)c1)C=C1N=CN=C1C2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63.1 %

Procedure:
A mixture of 0.2 g (0.87 mmol) of 8-chloroimidazo[4,5-g]quinoline-7-carbonitrile, 0.12 mL (1.1 mmol) of 3-bromoaniline, and 0.1 g (0.87 mmol) of pyridine hydrochloride in 5.0 mL of 2-ethoxyethanol is heated at reflux temperature for 45 minutes, then cooled to room temperature. The product mixture is poured into a saturated solution of sodium bicarbonate and stirred for 0.5 hour. The solid is collected by filtration, washed with water and dried. The solid is purified by silica gel chromatography, utilizing a gradient of methylene chloride/methanol (98:2 to 93:7) to yield 0.20 g of 8-(3-bromo-phenylamino)imidazo[4,5-g]quinoline-7-carbonitrile as pink solid, mp 286–288° C.
Reaction SMILES: Cl[C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH2:8][N:9]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[CH:3]=1.[NH2:26][CH:27]([CH2:30][OH:31])[CH2:28][OH:29].CN1CCCC1=[O:38]>>[CH:30]([OH:31])=[O:38].[Cl:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[N:9]1[C:10]2[C:5](=[C:4]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])[CH:3]=[C:2]([NH:26][CH:27]([CH2:30][OH:31])[CH2:28][OH:29])[N:11]=2)[CH:6]=[CH:7][C:8]1=[O:38]
Reactant: Clc1cc(-c2ccccc2Cl)c2c(n1)N(c1ccccc1Cl)CC=C2
Reactant: CN1CCCC1=O
Reactant: NC(CO)CO
Product: O=CO
Product: O=c1ccc2c(-c3ccccc3Cl)cc(NC(CO)CO)nc2n1-c1ccccc1Cl
Yield: 36 %

Procedure:
7-chloro-1,5-bis(2-chlorophenyl)[1,8]naphthyridin-2(1 h-one (73 mg, 0.182 mmol) and serinol (75 mg, 0.823 mmol) were dissolved in N-methylpyrrolidinone (2 ml) and heated in a Smith Creator microwave at 220° for 30 min. The mixture was evaporated in vacuo using a vacuum centrifuge, and the residue purified by mass directed autoprep HPLC (per general procedure B) to afford the title compound as a white solid (33 mg, 36%) NMR (400 MHz, CDCl3) δ 7.65-7.55 (2H,m), 7.52-7.42 (4H,m), 7.40-7.29 (3H,m), 6.40 (1H,s), 6.35 (1H,dd), 3.55-3.42 (5H,m)
Reaction SMILES: CN([C:4]([O:8]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl[C:24]1[CH:41]=[CH:40][C:27]([C:28]([NH:30][C:31]2C=C(C=CC=2)C(O)=O)=[O:29])=[C:26](OC)[CH:25]=1.Cl.CNOC.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:4][O:8][N:30]([CH3:31])[C:28](=[O:29])[C:27]1[CH:26]=[CH:25][CH:24]=[CH:41][CH:40]=1
Reactant: COc1cc(Cl)ccc1C(=O)Nc1cccc(C(=O)O)c1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: CNOC
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CON(C)C(=O)c1ccccc1
Reaction time: 2.5 h

Procedure:
TBTU (4.73 g, 14.7 mmol) was added to a solution of 3-{(4-chloro-2-methoxybenzoyl)amino}benzoic acid (4.50 g, 14.7 mmol), N,O-dimethylhydroxylamine hydrochloride (1.72 g, 17.7 mmol) and i-Pr2NEt (7.60 g, 58.9 mmol) in DMF (29 mL) at 25°. The reaction mixture was stirred at 25° for 2.5 h. The mixture was diluted with EtOAc (200 mL). The resulting solution was successively washed with aqueous 1 N HCl (2×75 mL), water (2×75 mL), aqueous saturated NaHCO3 (2×75 mL) and brine (75 mL), then dried (MgSO4), filtered and concentrated under reduced pressure to give the corresponding N-methoxy-N-methylbenzamide of formula 6 (4.32 g, 84% yield) as a white solid:
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[N:14]#[C:15]Br>C(Cl)Cl>[C:15]([N:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]1)#[N:14]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: N#CBr
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(C#N)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 54.6 %

Procedure:
To a solution of 1-Boc-piperazine (25 g, 0.13 mol) in anhydrous DCM (500 mL) at 0° C. was added TEA (52 mL, 0.40 mol) followed by a solution of cyanogen bromide (28.5 g, 0.27 mol) in anhydrous DCM (250 mL) slowly over a period of 30 min. The reaction mixture was stirred at RT for 16 hours and washed with a 10% aqueous solution of sodium bicarbonate, water and brine. The organic layer was dried and the solvent was removed under vacuum. The residue was purified by chromatography using chloroform/methanol (95/5) as eluent to afford 15 g (57%) of the title compound as a solid. TLC—Chloroform/methanol (9/1): Rf=0.7.
Reaction SMILES: [NH2:1][C:2](=[N:36][C:37](=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:23]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=2[F:35])[C:11]2[NH:15][C:14](=[O:16])[N:13]([C:17]3[N:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:12]=2)=[CH:5][CH:4]=1.C(=O)([O-])O.[K+].[CH3:50][C@@H:51]([O:55][C:56](=[O:61])[O:57][CH:58](Cl)[CH3:59])[CH2:52][CH2:53][CH3:54]>CN(C=O)C>[CH3:50][C@@H:51]([O:55][C:56](=[O:61])[O:57][CH:58]([O:16][C:14]1[N:13]([C:17]2[N:18]=[CH:19][CH:20]=[CH:21][N:22]=2)[N:12]=[C:11]([CH:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([C:2]([NH2:1])=[N:36][C:37](=[O:44])[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)=[CH:4][CH:5]=2)[C:23]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=2[F:35])[N:15]=1)[CH3:59])[CH2:52][CH2:53][CH3:54]
Reactant: COc1cc(OCCO)c(F)c(C(Nc2ccc(C(N)=NC(=O)c3ccccc3)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c1
Reactant: CCC[C@@H](C)OC(=O)OC(C)Cl
Agent: O=C([O-])O
Agent: [K+]
Solvent: CN(C)C=O
Product: CCC[C@@H](C)OC(=O)OC(C)Oc1nc(C(Nc2ccc(C(N)=NC(=O)c3ccccc3)cc2)c2cc(OC)cc(OCCO)c2F)nn1-c1ncccn1
Temperature: 55 °C
Reaction time: 18 h
Yield: 68.6 %

Procedure:
To a mixture of N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 1a, 150 mg) and DMF (3 mL), potassium hydrogen carbonate (150 mg) and carbonic acid 1-chloroethyl ester (R)-1-methylbutyl ester (150 mg) were sequentially added, and the resulting mixture was stirred at 55° C. for 18 hours. The reaction mixture was purified by reverse phase silica gel column chromatography (mixed solvent of acetonitrile-water) to obtain the captioned compound (130 mg).
Reaction SMILES: [C:1]([C:3]1[CH:15]=[CH:14][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:5][CH:4]=1)#[N:2].Cl[CH2:17][CH2:18][S:19][S:20][CH2:21][CH2:22]Cl.[OH-].[K+]>CS(C)=O>[CH2:17]([N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:6]2[CH:14]=[CH:15][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH2:9][CH2:10]1)[CH2:18][S:19][S:20][CH2:21][CH2:22][N:11]1[CH2:12][CH2:13][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:15][CH:14]=2)[CH2:9][CH2:10]1
Reactant: ClCCSSCCCl
Reactant: N#Cc1ccc(CN2CCNCC2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: N#Cc1ccc(CN2CCN(CCSSCCN3CCN(Cc4ccc(C#N)cc4)CC3)CC2)cc1
Temperature: 80 °C
Reaction time: 8 h
Yield: 85 %

Procedure:
A mixture of 4-cyanobenzylpiperazine (4.0 g), bis(2-chloroethyl) disulfide (1.9 g), potassium hydroxide (5.0 g), and dimethylsulfoxide (50 ml) is heated at 80° C. until the solution turns pink in color. The heat is then removed and the reaction mixture allowed to stir overnight at room temperature. The solution is diluted with water, and the product extracted with ether, dried, and concentrated to give 4.4 g of an oil, which is purified on a silica gel column (methylene chloride: methanol, 98:2). The resulting light brown oil is dissolved in ether and the salt precipitated with ethereal hydrochloric acid to give, after recrystallization from aqueous ethanol, 1,1'-(dithiodi-2,1-ethanediyl)bis[4-(4-cyanobenzyl)piperazine] tetrahydrochloride as a white crystalline solid, m.p. 272°-275° C.
Reaction SMILES: C[O-].[Ca+2:3].C[O-].[C:6]([OH:11])(=[O:10])[C:7]([CH3:9])=[CH2:8].[C:12]([OH:31])(=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>O1CCCC1>[C:6]([O-:11])(=[O:10])[C:7]([CH3:9])=[CH2:8].[C:12]([O-:31])(=[O:30])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].[Ca+2:3]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: C=C(C)C(=O)O
Agent: C[O-]
Agent: [Ca+2]
Solvent: C1CCOC1
Product: C=C(C)C(=O)[O-]
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]
Reaction time: 8 h

Procedure:
1.02 Grams of calcium (II) methoxide (0.01 mol) was weighed in a round bottom flask in a dry box. A mixture of 0.875 g of (0.01 mol) of methacrylic acid and 2.930 g (0.01 mol) of oleic acid was mixed in 19 g of dry tetrahydrofuran. This acid-mixture was introduced into a round bottom flask which was purged with argon. The contents were magnetically stirred overnight (20 hr) at ambient temperature. The volatile matter was then removed in vacuo (0.1 mm Hg) for 10 hours at room temperature. The resulting solid was analyzed for its metal content.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[OH:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=3)=[O:44])[CH2:36][CH2:35]2)=[O:33])[CH2:15]1>O1CCCC1>[CH3:8][S:9]([O:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=3)=[O:44])[CH2:36][CH2:35]2)=[O:33])[CH2:15]1)(=[O:11])=[O:10]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(OCCN1CCN(C(=O)[C@@H]2C[C@@H](O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CS(=O)(=O)O[C@@H]1C[C@@H](C(=O)N2CCN(CCOC(=O)OCc3ccc([N+](=O)[O-])cc3)CC2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Reaction time: 0.5 h

Procedure:
89 μl of triethylamine and 50 μl of methanesulfonyl chloride were added to a solution of 321 mg of (2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine in 3.2 ml of anhydrous tetrahydrofuran, whilst ice-cooling, and the resulting mixture was stirred at 0° to 5° C. for 30 minutes and then at room temperature for 1 hour. The reaction mixture was then concentrated by evaporation under reduced pressure, and the residue was mixed with an aqueous solution of sodium hydrogencarbonate and then extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate; the solvent was then removed by distillation under reduced pressure, to afford 345 mg of the title compound as a powder.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:35][O:36][C:37]1[C:42]2[N:43]=[C:44]([NH2:46])[O:45][C:41]=2[C:40]([CH:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[CH:39][CH:38]=1>C1COCC1.O1CCOCC1.CN(C=O)C>[CH3:35][O:36][C:37]1[C:42]2[N:43]=[C:44]([NH:46][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][N:10]=[C:2]([CH3:1])[CH:3]=3)[O:45][C:41]=2[C:40]([CH:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[CH:39][CH:38]=1
Reactant: COc1ccc(C2CCOCC2)c2oc(N)nc12
Reactant: Cc1cc(C(=O)O)ccn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: COc1ccc(C2CCOCC2)c2oc(NC(=O)c3ccnc(C)c3)nc12

Procedure:
From 2-methylisonicotinic acid, HATU and N-diethylisopropylamine in THF, then treatment with 4-methoxy-7-(tetrahydro-pyran-4-yl)-benzooxazol-2-yl-amine in dioxane and DMF. ES-MS m/e (%): 368 (M+H+, 100).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([N+:9]([O-])=O)[CH:6]=[C:5]([Br:12])[C:3]=1[NH2:4].C(OCC)(=O)C.CN(C)C=O.[H][H]>C(O)C.[Pt]>[NH2:4][C:3]1[C:2]([Br:1])=[CH:8][C:7]([NH2:9])=[CH:6][C:5]=1[Br:12]
Reactant: Nc1c(Br)cc([N+](=O)[O-])cc1Br
Reactant: [H][H]
Agent: [Pt]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: CCOC(C)=O
Product: Nc1cc(Br)c(N)c(Br)c1

Procedure:
3.0 g of 2,6-dibromo-4-nitroaniline are dissolved in 150 ml of ethanol, 150 ml of ethyl acetate and 30 ml of dimethylformamide and, after addition of 0.5 g of platinum on carbon (5%), hydrogenated under a pressure of 1.5 bar of hydrogen in a Parr apparatus at room temperature for 1 hour. Cooling is followed by filtration, the solvent is distilled off in a rotary evaporator, and the residue is purified by column chromatography.
Reaction SMILES: [CH2:1]([N:5]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[C:8]([OH:14])[CH:7]=1)[CH2:2][CH2:3][CH3:4].N1C=CN=C1.[C:24]([Si:28](Cl)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH3:27])([CH3:26])[CH3:25].O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([N:5]([CH2:15][CH2:16][CH2:17][CH3:18])[C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[C:8]([O:14][Si:28]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(CCCC)c1ccc(C=O)c(O)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: CCCCN(CCCC)c1ccc(C=O)c(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1
Temperature: 25 °C
Yield: 97.7 %

Procedure:
In 40 ml of N,N-dimethylformamide were dissolved 5.39 g (21.6 mmol) of 4-dibutylamino-2-hydroxybenzaldehyde and 4.08 g (60.0 mmol) of imidazole. Next, 6.13 g (22.3 mmol) of tert-butylchlorodiphenylsilane was added dropwise thereto with stirring at room temperature. The mixture was stirred for 3.5 hours. After the reaction mixture was poured into water, extraction with ethyl acetate, washing with a saturated saline solution, drying over anhydrous sodium sulfate, and concentration were performed. The residue was purified by silica gel column chromatography to give 10.3 g of a colorless oily matter (yield: 97.7%).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH:21]([NH2:23])[CH3:22])[CH:17]=[CH:18][CH:19]=1.C(N(CC)CC)C>C1C=CC=CC=1>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([NH:23][CH:21]([CH3:22])[CH2:20][C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([O:13][CH3:12])[CH:15]=2)(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1cccc(CC(C)N)c1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: COc1cccc(CC(C)NS(=O)(=O)c2ccc(C)cc2)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of p-toluenesulfonyl chloride (28.8 gm., 0.15 M) in benzene (100 ml.) was added dropwise to a solution of 2-(3-methoxyphenyl)-1-methylethylamine (23 gm., 0.139 M) and triethylamine (13 gm., 0.15 M) in benzene (200 ml.) during 30 minutes. The reaction was stirred at room temperature for 4 hours. The precipitated triethylamine hydrochloride was filtered off and the benzene solution was washed with hydrochloric acid (3 N), water and saturated brine. The benzene solution was dried over magnesium sulfate. Evaporation of the solvent afforded N-toluene-p-sulfonyl-2-(3-methoxyphenyl)-1-methylethylamine as an oil. Wt=42 gm.
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[CH:4]([CH:5]([OH:13])[C:6]([Cl:12])([Cl:11])[C:7]([F:10])([F:9])[F:8])[CH:3]1[C:14]([O:16][CH3:17])=[O:15].[C:19](OC(=O)C)(=[O:21])[CH3:20]>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:18])[CH:4]([CH:5]([O:13][C:19](=[O:21])[CH3:20])[C:6]([Cl:11])([Cl:12])[C:7]([F:8])([F:9])[F:10])[CH:3]1[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)C1C(C(O)C(Cl)(Cl)C(F)(F)F)C1(C)C
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: COC(=O)C1C(C(OC(C)=O)C(Cl)(Cl)C(F)(F)F)C1(C)C
Reaction time: 8 h
Yield: 93 %

Procedure:
To 50 mg (0.16 mmol) of methyl 2,2-dimethyl-3-(1-hydroxy-2,2-dichloro-3,3,3-trifluoropropyl)cyclopropanecarboxylate obtained in Example 1, 0.2 ml of acetic anhydride and 0.2 ml of pyridine were added, and the mixture was left overnight at room temperature. In the same manner as in Example 9, 53 mg of methyl 2,2-dimethyl-3-(1-acetoxy-2,2-dichloro-3,3,3-trifluoropropyl)cyclopropanecarboxylate was obtained as a colorless oily substance. Yield: 93%. The physical property values were the same as those in Example 7.