Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.[CH:21]1[C:30]2[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=2[CH:24]=[CH:23][N:22]=1>CCOCC>[Br-:1].[N:17]1[CH:18]=[CH:19][CH:20]=[C:15]([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N+:22]2[CH:23]=[CH:24][C:25]3[CH2:26][CH2:27][CH2:28][CH2:29][C:30]=3[CH:21]=2)[CH:16]=1
Reactant: c1cc2c(cn1)CCCC2
Reactant: BrCCCCCCCCCCCCCc1cccnc1
Solvent: CCOCC
Product: [Br-]
Product: c1cncc(CCCCCCCCCCCCC[n+]2ccc3c(c2)CCCC3)c1
Yield: 62 %

Procedure:
3-(13-Bromo-tridecyl)-pyridine (1 mmol) was added to 5,6,7,8-tetrahydro-isoquinoline (5 ml), and the mixture was heated at 50 C overnight. The resulting residue was treated with ether, and the ether was decanted after deposition for 30′. The residue was partitioned between water and ether. The aqueous layer was washed extensively with ether, and then the aqueous layer was extracted with chloroform. The chloroform was removed to afford the product (62%). 1HNMR (300 MHz, CDCl3, ppm), 9.22 (s, 1H), 8.90 (d, J=6.3, 1H), 8.44 (br, 2H), 7.67 (d, J=6.3, 1H), 7.55 (d, 8.1, 7.24-7.28 (m, 1H), 4.83 (t, J=7.2, 2.98-3.01 (m, 4H), 2.60 (t, J=7.8, 2H), 1.94-2.02 (m, 2H), 1.87-1.90 (m, 4H), 1.56-1.60 (m, 2H), 1.19-1.35 (br, 20H); 13CNMR, 157.87, 148.79, 146.13, 144.20, 140.68, 138.95, 138.80, 137.26, 128.08, 123.92, 61.40, 58.62, 33.30, 32.20, 31.34, 29.94, 29.82, 29.77, 29.67, 29.42, 29.36, 26.71, 26.46, 21.40, 18.81.
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=[O:4].[CH:30]([C:32]1[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:29][C:2]([F:28])([F:1])[C:3]([N:5]([CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:30][C:32]2[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=2)[CH2:9][CH2:8]1)[C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=2)=[CH:18][CH:17]=1)=[O:4]
Reactant: COC(=O)c1ccc(C=O)cc1
Reactant: Cn1cc(-c2ccc([C@@H]3C[C@H]3N(CC3CCNCC3)C(=O)C(F)(F)F)cc2)cn1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: COC(=O)c1ccc(CN2CCC(CN(C(=O)C(F)(F)F)[C@@H]3C[C@H]3c3ccc(-c4cnn(C)c4)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 58.7 %

Procedure:
To a solution of 2,2,2-trifluoro-N-(trans-2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (85 mg, 0.209 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 4-formylbenzoate (41.2 mg, 0.251 mmol) and sodium triacetoxyborohydride (75 mg, 0.356 mmol), and the mixture was stirred at room temperature for 18 h. The mixture was quenched with water (3 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 100% EtOAc/hexanes) to give 68 mg of product as off-white solid. MS: (M+H)+=555.3. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.28-1.53 (m, 4H), 1.56-1.76 (m, 3H), 1.80-1.96 (m, 1H), 1.98-2.11 (m, 3H), 2.44 (br. s., 1H), 2.75-2.97 (m, 3H), 3.09-3.19 (m, 1H), 7.12 (d, J=8.08 Hz, 2H), 7.41-7.55 (m, 5H), 7.91-8.03 (m, 3H)
Reaction SMILES: N[N:2]1[C:6](=[O:7])[C:5]([CH3:8])=[C:4]([CH3:9])[C:3]1=[O:10].C([N:13]([CH2:16][CH3:17])CC)C.[C:18](Cl)(=[O:22])[C:19](C)=C>ClCCl>[NH2:13][C:16](=[CH2:17])[C:18](=[O:22])[CH2:19][N:2]1[C:6](=[O:7])[C:5]([CH3:8])=[C:4]([CH3:9])[C:3]1=[O:10]
Reactant: C=C(C)C(=O)Cl
Reactant: CC1=C(C)C(=O)N(N)C1=O
Reactant: CCN(CC)CC
Solvent: ClCCl
Product: C=C(N)C(=O)CN1C(=O)C(C)=C(C)C1=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
140.0 g (1.0 mol) of N-amino-dimethylmaleimide and 111.3 g (1.1 mols) of triethylamine (dried over NaOH) are dissolved in 2,500 ml of dichloromethane and the solution is cooled to 0° C. 104.5 g (1.0 mol) of methacrylic acid chloride are allowed to run dropwise into this solution at such a rate that the temperature does not 10° C. When the reaction has ended, the mixture is heated to 40° C. and then stirred for one hour at this temperature.
Reaction SMILES: [CH3:1][N:2]1[C:6]([N:7]2[CH:11]=[CH:10][CH:9]=[CH:8]2)=[C:5]([C:12]([OH:14])=O)[CH:4]=[N:3]1.N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:23]>ClCCl>[CH3:1][N:2]1[C:6]([N:7]2[CH:11]=[CH:10][CH:9]=[CH:8]2)=[C:5]([C:12]([F:23])=[O:14])[CH:4]=[N:3]1
Reactant: Cn1ncc(C(=O)O)c1-n1cccc1
Reactant: Fc1nc(F)nc(F)n1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cn1ncc(C(=O)F)c1-n1cccc1
Reaction time: 2 h

Procedure:
To a stirred solution of 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid (7.65 g, 40 mmol) in dry dichloromethane (150 mL) and pyridine (3.2 mL, 40 mmol) under a nitrogen atmosphere was added cyanuric fluoride (5.4 g, 40 mmol) at 0° C. The reaction mixture was stirred for two hours during which time the reaction temperature was allowed to rise to room temperature. Crushed ice was then added along with additional dichloromethane. The organic layer was separated and the aqueous layer was extracted twice with dichloromethane. Concentration of the combined organic layers under reduced pressure gave 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carbonyl fluoride which was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:14])=O>CN(C=O)C.C(#N)C>[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([Cl:14])=[O:5]
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1ncccc1C(=O)O
Solvent: CN(C)C=O
Solvent: CC#N
Product: Cc1ncccc1C(=O)Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 103.5 %

Procedure:
To an acetonitrile solution (5 ml) of 2-methylnicotinic acid (400 mg, 2.92 mmol) and DMF (11.2 μl, 0.156 mmol), oxalyl dichloride (501 μl, 5.83 mmol) was added dropwise, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, to obtain a crude product of 2-methylnicotinic acid chloride as a yellow liquid (470 mg).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[N:9]=[N:10][C:11](Cl)=[CH:12][C:13]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:24]=[N+:25]=[N-:26].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([C:8]1[N:9]=[N:10][C:11]([N:24]=[N+:25]=[N-:26])=[CH:12][C:13]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[F:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)c1nnc(Cl)cc1Nc1ccc(Br)cc1F
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)c1nnc(N=[N+]=[N-])cc1Nc1ccc(Br)cc1F
Temperature: 25 °C

Procedure:
To a solution of 4-(4-bromo-2-fluoro-phenylamino)-6-chloro-pyridazine-3-carboxylic acid tert-butyl ester (300 mg, 034 mmol) in DMF (5 ml) under argon at room temperature is added sodium azide (96 mg, 1.48 mmol) with stirring. The reaction mixture is stirred at 50° C. for 6 hours. After cooling to room temperature, the reaction mixture is diluted with ethyl acetate and washed with water, saturated NaHCO3 (20 ml×3) and saturated NaCl (30 ml×3). The organic layer is dried over Na2SO4 and concentrated. The residue is purified by flash column chromatography to provide the desired product.
Reaction SMILES: Cl[CH2:2][C:3](=O)/[CH:4]=[CH:5]/[C:6]([O:8][CH2:9][CH3:10])=[O:7].[Cl:12][C:13]1[CH:29]=[CH:28][C:16]([C:17]([N:19]2[CH2:23][CH2:22][CH:21]([NH:24][C:25]([NH2:27])=[S:26])[CH2:20]2)=[O:18])=[CH:15][CH:14]=1>C(#N)C>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]([N:19]2[CH2:23][CH2:22][CH:21]([NH:24][C:25]3[S:26][CH:2]=[C:3](/[CH:4]=[CH:5]/[C:6]([O:8][CH2:9][CH3:10])=[O:7])[N:27]=3)[CH2:20]2)=[O:18])=[CH:28][CH:29]=1
Reactant: CCOC(=O)/C=C/C(=O)CCl
Reactant: NC(=S)NC1CCN(C(=O)c2ccc(Cl)cc2)C1
Solvent: CC#N
Product: CCOC(=O)/C=C/c1csc(NC2CCN(C(=O)c3ccc(Cl)cc3)C2)n1
Temperature: 70 °C
Reaction time: 3 h
Yield: 87.4 %

Procedure:
The mixture of ethyl (2E)-5-chloro-4-oxo-2-pentenoate (0.5 g) and N-[1-(4-chlorobenzoyl)-3-pyrrolidinyl]thiourea (0.8 g) in acetonitrile (10 mL) was stirred at 70° C. for 3 hours, and the mixture was evaporated in vacuo. To the residue was added a solution of AcOEt and water, and the mixture was adjusted to pH 8 with 20% aqueous potassium carbonate. The separated organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel using AcOEt as an eluent. The eluted fractions containing the desired product were collected and evaporated in vacuo to give ethyl (2E)-3-(2-{[1-(4-chlorobenzoyl)-3-pyrrolidinyl]amino}-1,3-thiazol-4-yl)acrylate (1.0 g).
Reaction SMILES: C[O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[CH3:14].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([CH2:45][CH3:46])(=[O:44])=[O:43])=[CH:38][C:37]=1[C:47]([F:50])([F:49])[F:48]>CN(C=O)C>[CH2:45]([S:42]([C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:2])=[O:15])=[C:6]2[CH3:14])=[C:37]([C:47]([F:49])([F:48])[F:50])[CH:38]=1)(=[O:43])=[O:44])[CH3:46]
Reactant: CCS(=O)(=O)c1ccc(CBr)c(C(F)(F)F)c1
Reactant: COC(=O)Cc1c(C)[nH]c2ncccc12
Agent: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Solvent: CN(C)C=O
Product: CCS(=O)(=O)c1ccc(Cn2c(C)c(CC(=O)O)c3cccnc32)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of (2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetic acid methyl ester (0.77 g, 3.78 mmol) in dry DMF (12 ml) under an inert atmosphere of Argon is added dropwise, BEMP (1.75 ml, 6.04 mmol). The mixture was allowed to stir at room temperature for 1 hour and then treated with 1-bromomethyl-4-ethanesulfonyl-2-trifluoromethyl-benzene (2 g, 6.04 mmol). Stirring continues for a further 2 hours after which time, the reaction mixture is partitioned between ethyl acetate/diethyl ether (80 ml of a 1:1 mixture) and water (100 ml). The organic portion is separated and washed with brine and concentrated in vacuo. Purification of the crude by chromatography on silica eluting with iso-hexane/ethyl acetate (3:1 increasing to 2:1) yields the titled product. (MH+ 455)
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)[Cl:2].[C:7]([CH:13]([C:16]#[N:17])[C:14]#[N:15])(=O)[C:8]([CH3:11])([CH3:10])[CH3:9].S(=O)=O>C(Cl)Cl>[Cl:2][C:7]([C:8]([CH3:11])([CH3:10])[CH3:9])=[C:13]([C:16]#[N:17])[C:14]#[N:15]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: CC(C)(C)C(=O)C(C#N)C#N
Agent: O=S=O
Solvent: ClCCl
Product: CC(C)(C)C(Cl)=C(C#N)C#N
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Phosphorous pentachloride (86 g) was added slowly to a stirred suspension of the above pivaloylmalononitrile intermediate (a) (57 g) in methylene chloride (500 ml) and was allowed to stir at room temperature for 16 hours. Sulfur dioxide was passed through the solution for 20 minutes and the solvent was removed on a rotary evaporator. The residue was poured onto ice and filtered. The product was used without further purification.
Reaction SMILES: C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:15]([O:18][CH:19]([CH3:21])[CH3:20])[CH:16]=[N:17][C:10]=2[N:9]([CH3:29])[C:8]1=[O:30])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[CH2:22]([C:14]1[C:11]2[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:30])[N:9]([CH3:29])[C:10]=2[N:17]=[CH:16][C:15]=1[O:18][CH:19]([CH3:21])[CH3:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)Oc1cnc2c(c1Cc1ccccc1)c(=O)n(CCCOC=O)c(=O)n2C
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)Oc1cnc2c(c1Cc1ccccc1)c(=O)n(CCCO)c(=O)n2C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 27.6 %

Procedure:
To a solution of 3-(5-benzyl-6-isopropoxy-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (70 mg, 0.17 mmol) in THF (1 mL) and water (1 mL) was added LiOH.H2O (14.2 mg, 0.34 mmol). The reaction was stirred at RT for 15 min then diluted with EA (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-benzyl-3-(3-hydroxypropyl)-6-isopropoxy-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (18 mg, 39.0% yield) as a white solid. 1H NMR (CDCl3) δ: 8.32 (s, 1H), 7.25-7.18 (m, 4H), 7.17-7.10 (m, 1H), 4.78 (s, 2H), 4.62 (dt, J=12.1, 6.1 Hz, 1H), 4.26-4.15 (m, 2H), 3.69 (s, 3H), 3.52-3.43 (m, 2H), 3.17 (t, J=7.0 Hz, 1H), 1.94-1.82 (m, 2H), 1.34 (d, J=6.0 Hz, 6H). LCMS: MH+ 384 and TR=2.708 min.
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C:7]([CH3:10])([CH3:9])[CH3:8])=[O:4].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[Br:42][C:43]1[CH:51]=[CH:50][C:46]([CH2:47][NH:48][NH2:49])=[CH:45][CH:44]=1>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@H:6]([C:11]([NH:49][NH:48][CH2:47][C:46]1[CH:50]=[CH:51][C:43]([Br:42])=[CH:44][CH:45]=1)=[O:13])[C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: NNCc1ccc(Br)cc1
Reactant: COC(=O)N[C@H](C(=O)O)C(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN1CCOCC1
Product: COC(=O)N[C@H](C(=O)NNCc1ccc(Br)cc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 54 %

Procedure:
N-(Methoxycarbonyl)-(L)-tert-leucine (J. Med. Chem., 41, 3387-3401, 1998) (1.74 g, 9.20 mmol) was dissolved in EtOAc (50 mL) and EDAC (1.94 g, 10.1 mmol), HOBT (1.37 g, 10.1 mmol), and NMM (1.11 mL, 10.1 mmol) were added. The reaction mixture was stirred at room temperature for 30 min and then 4-bromo-benzylhydrazine (prepared as described in Zh. Org. Khim., 28, 43-50, 1992) (2.31 g, 11.5 mmol) in EtOAc (20 mL) was added and the stirring was continued over night. The reaction mixture was washed with saturated NaHCO3 (aq.), H2O and brine and then the organic phase was dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-96:4) yielding the title compound (1.85 g, 54%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[CH2:10]Cl.[C-:12]#[N:13].[Na+]>C(O)C.O>[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[C:3]=1[CH2:10][C:12]#[N:13]
Reactant: [C-]#N
Reactant: ClCc1c(Cl)cc(Cl)cc1Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: N#CCc1c(Cl)cc(Cl)cc1Cl
Yield: 69.4 %

Procedure:
To a stirred solution of 1,3,5-trichloro-2-chloromethyl-benzene (12.85 g, 58.8 mmole) in ethanol (45 ml), NaCN (3.20, 67.0 mmole) solution in water (15 ml) was added at ambient temperature. The reaction mixture was refluxed for 4 hours to complete the reaction. Ethanol was evaporated and the reaction mixture was diluted with water (50 ml). The aqueous layer was extracted with EtOAc (3×100 ml). The combined organic layer was washed with brine (30 ml) and dried over sodium sulfate. Organic layer was concentrated under vacuum to give white solid. Crude product was purified by chromatography on silica-gel column to afford 9.0 g (75.0% of theory) of (2,4,6-trichloro-phenyl)-acetonitrile
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[CH:15][N:16]=[CH:17][C:18](Br)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OCC)C.C([Li])CCC.[CH2:30]([Sn:34](Cl)([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])[CH2:31][CH2:32][CH3:33]>C1COCC1.C1CCCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[CH:15][N:16]=[CH:17][C:18]([Sn:34]([CH2:35][CH2:36][CH2:37][CH3:38])([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:30][CH2:31][CH2:32][CH3:33])=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: O=S(=O)(c1ccccc1)n1ccc2c(Br)cncc21
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: C1CCCCC1
Product: CCCC[Sn](CCCC)(CCCC)c1cncc2c1ccn2S(=O)(=O)c1ccccc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
1-Benzenesulfonyl-4-bromo-1H-pyrrolo[2,3-c]pyridine (0.34 g, 1.0 mmol) was dissolved in THF (5 mL) and diethyl ether (5 mL) and the solution cooled to −78° C. n-Butyllithium (0.756 M in hexanes, 1.2 mL, 5.0 mmol) was added over 5 min then the mixture was stirred for 15 min before addition of tributyltin chloride (0.39 g, 1.2 mmol) over 10 min. The reaction mixture was stirred at −78° C. for 1 hour then allowed to warm to room temperature and diluted with cyclohexane (50 mL). The reaction mixture was washed with water (3×30 mL) followed by brine, before the organic phase was dried (MgSO4) and evaporated. The crude residue was purified by chromatography on alumina using 30% EtOAc in cyclohexane. The material was further purified by flash chromatography (Si—PPC), eluting with 5-10% EtOAc in cyclohexane to yield the title product. 1H NMR (CDCl3, 300 MHz): δ 9.23 (s, 1H), 8.36 (s, 1H), 7.91-8.00 (m, 2H), 7.71, d, J=1.1 Hz, 1H), 7.55-7.63 (m, 1H), 7.42-7.53 (m, 2H), 6.59 (d, J=1.1 Hz, 1H), 1.45-1.65 (m, 6H), 1.21-1.38 (m, 6H), 1.09-1.20 (m, 6H), 0.85 (t, J=7.5 Hz, 9H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:15]([CH3:19])([CH3:18])[C:16]#[CH:17].CCN(CC)CC.Cl>[Cu]Cl.O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:15]([CH3:19])([CH3:18])[C:16]#[CH:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C#CC(C)(C)Cl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: Cl[Cu]
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: O
Product: C#CC(C)(C)N1CCN(C(=O)OC(C)(C)C)CC1
Yield: 77.1 %

Procedure:
To a stirred mixture of 1-tert-butyloxycarbonylpiperazine (1.10 g, 5.91 mmol), 3-chloro-3-methyl-1-butyne (0.88 ml, 7.81 mmol), THF (10 ml), and NEt3 (1.10 ml, 7.91 mmol) under nitrogen was added copper(I) chloride (45 mg, 0.46 mmol). An exothermic reaction ensued and a precipitate formed. After stirring for 0.5 hours at room temperature water (20 ml) and 1 N aqueous hydrochloric acid (8 ml) were added and the mixture was concentrated under reduced pressure to ⅔ of its original volume. The mixture was washed with ethyl acetate (2×20 ml) and made basic by addition of potassium carbonate (approx. 4 g). Extraction with ethyl acetate (3×20 ml), washing of the combined extracts (30 ml brine), drying with magnesium sulphate, and concentration under reduced pressure yielded 1.15 g (77%) of the title compound as a colourless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15].[Br:34][C:35]1[S:39][C:38]([C:40](Cl)=[O:41])=[CH:37][CH:36]=1>>[Br:34][C:35]1[S:39][C:38]([C:40]([C:4]2[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[Cl:1])[N:6]([C@@H:11]3[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]3[O:13][C:14](=[O:16])[CH3:15])[CH:5]=2)=[O:41])=[CH:37][CH:36]=1
Reactant: O=C(Cl)c1ccc(Br)s1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc3c(Cl)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(C(=O)c3ccc(Br)s3)c3c(Cl)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
4-Chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole obtained in Example 1-(3) and 5-bromothiophene-2-carbonyl chloride were treated in a manner similar to Example 2-(4) to give 4-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indol-3-yl 5-bromo-2-thienyl ketone as a yellow powder. APCI-Mass m/Z 670/672 (M+H). 1H-NMR (DMSO-d6) δ 1.67 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 2.05 (s, 3H), 4.11 (d, J=4.0 Hz, 2H), 4.30 (ddd, J=9.8, 4.2 and 3.9 Hz, 1H), 5.30 (t, J=9.8 Hz, 1H), 5.55 (t, J=9.6 Hz, 1H), 5.81 (t, J=9.3 Hz, 1H), 6.36 (d, J=9.0 Hz, 1H), 7.30 (d, J=7.5 Hz, 1H), 7.39 (t, J=8.0 Hz, 1H), 7.47 (d, J=3.9 Hz, 1H), 7.53 (d, J=4.0 Hz, 1H), 7.78 (d, J=8.3 Hz, 1H), 8.46 (s, 1H).
Reaction SMILES: [O:1]=[C:2]([C@H:4]([CH2:6][C:7]1[CH:14]=[C:12]([OH:13])[C:10]([OH:11])=[CH:9][CH:8]=1)[NH2:5])[OH:3].CO.[F:17][C:18]([F:24])([F:23])[C:19](OC)=[O:20]>O>[F:17][C:18]([F:24])([F:23])[C:19]([NH:5][C@@H:4]([CH2:6][C:7]1[CH:14]=[C:12]([OH:13])[C:10]([OH:11])=[CH:9][CH:8]=1)[C:2]([OH:3])=[O:1])=[O:20]
Reactant: COC(=O)C(F)(F)F
Reactant: N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O
Solvent: O
Solvent: CO
Product: O=C(O)[C@H](Cc1ccc(O)c(O)c1)NC(=O)C(F)(F)F
Reaction time: 0.17 h

Procedure:
1.97 g L-DOPA (10 mmol) and 5 ml of dry methanol was added into an oven-dried 25 ml round-bottomed flask equipped with a Teflon stirring bar and rubber septum and purged with dry argon. Then, 1.3 ml of TMG (10 mmol) and 1.4 ml of methyl trifluoroacetate (12.5 mmol) was added. The mixture was stirred vigorously at room temperature until DOPA had completely dissolved (after about 24 hr). At this point, the flask was immersed in cold water (0° C.) and 5 ml of methanol and 4 g Dowex 50 resin (H+ form) were added. The mixture was filtered after stirring for 10 min. The filtrate was evaporated under reduced pressure. The crude product was re-crystallized from ethyl acetate and the yield of N-trifluoroacetyl-L-DOPA was 78%. See Curphey, T. J. Trifluoroacetylation of amino acids and peptides by ethyl trifluoroacetate. J. Org. Chem. 1979, 44, 2805-2807; Lapidot, Y.; Rappoport, S.; Wolman, Y. Use of ester of N-hydroxysuccinimide in the synthesis of N-acrylamino acids. J. Lipid Research 1967, 8, 142-145.
Reaction SMILES: CCCCCCCCCCCCC.[H][H].[F:16][C:17]1[C:21]([F:23])([F:22])[C:20]([F:25])([F:24])[C:19]([F:27])([F:26])[CH:18]=1>[Pd]>[F:26][C:19]1([F:27])[CH2:18][CH:17]([F:16])[C:21]([F:22])([F:23])[C:20]1([F:24])[F:25].[F:22][C:21]1([F:23])[CH2:17][CH2:18][C:19]([F:27])([F:26])[C:20]1([F:24])[F:25]
Reactant: FC1=CC(F)(F)C(F)(F)C1(F)F
Reactant: [H][H]
Agent: [Pd]
Agent: CCCCCCCCCCCCC
Product: FC1(F)CCC(F)(F)C1(F)F
Product: FC1CC(F)(F)C(F)(F)C1(F)F
Temperature: 40 °C

Procedure:
One percent by weight of n-tridecane (dielectric constant 2.0), a low-polarity compound, was dissolved in crude 1,3,3,4,4,5,5-heptafluorocyclopentene having a purity of 99.9 GC %. An autoclave having a capacity of 100 ml was charged with a catalyst of activated carbon having supported thereon 5% by weight of powdered palladium. After the deaeration under reduced pressure, n-tridecane-containing 1,3,3,4,4,5,5-heptafluorocyclopentene prepared previously was poured. While the mixture was stirred at 40° C., the reaction was conducted by repeating block charge of hydrogen at a gauge pressure in the range of 0 to 6 kgf/cm2. After the completion of the reaction, the product was analyzed through gas chromatography. Consequently, a fluorinated saturated hydrocarbon containing 94 mol % of 1,1,2,2,3,3,4-heptafluorocyclopentane (HFCPA) and 6 mol % of 1,1,2,2,3,3-hexafluorocyclopentane was obtained.