Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(C[O:8][C:9](=[O:51])[CH2:10][N:11]([C:23]2[CH:28]=[C:27]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[CH:26]=[C:25]([C:48](=[O:50])[NH2:49])[CH:24]=2)[CH2:12][C:13]([O:15]CC2C=CC=CC=2)=[O:14])C=CC=CC=1.[H][H].CN(C=O)C>[Pd].C1COCC1>[C:9]([CH2:10][N:11]([C:23]1[CH:28]=[C:27]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])[CH:26]=[C:25]([C:48](=[O:50])[NH2:49])[CH:24]=1)[CH2:12][C:13]([OH:15])=[O:14])([OH:51])=[O:8]
Reactant: [H][H]
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(C(N)=O)cc(N(CC(=O)OCc2ccccc2)CC(=O)OCc2ccccc2)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCOc1cc(C(N)=O)cc(N(CC(=O)O)CC(=O)O)c1
Reaction time: 3 h
Yield: 69 %

Procedure:
A mixture of 2.2 g of N-[(3-carbamoyl)-5-(octadecyloxy)phenyl-N-[2-(phenylmethoxy)-2-oxoethyl]glycine phenylmethyl ester and 0.5 g of 10% palladium on carbon in 100 ml of THF was stirred in a hydrogen atmosphere at room temperature until uptake ceased after 3 hours. DMF (150 ml) was added and the mixture was heated to dissolve the precipitated product. The hot mixture was filtered to remove the catalyst and the filtrate was concentrated at reduced pressure to a solid. Recrystallization from THF gave 1.1 g (69% yield, mp 213°-216°) of N-(carboxymethyl)-N-[(3-carbamoyl)-5-(octadecyloxy)phenyl]glycine.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][C:7](=[O:16])[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.CCN(CC)CC.[Si]([I:28])(C)(C)C.II>C(Cl)Cl>[I:28][N:6]1[C:7](=[O:16])[CH2:8][C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[C:11]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]1=2
Reactant: C[Si](C)(C)I
Reactant: O=C1Cc2ccccc2-c2ccccc2N1
Agent: II
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1Cc2ccccc2-c2ccccc2N1I
Temperature: 7.5 °C

Procedure:
A solution of 5,7-dihydro-6H-dibenz[b,d]azepin-6-one (1.0 g, 4.77 mmol) (Example 3-A) and Et3N (2.66 mL, 19.12 mmol) were stirred for 5.0 minutes at −15° C. in CH2Cl2 and treated with TMSI (1.36 mL, 9.54 mmol). After stirring for 15 minutes I2 (1.81 g, 7.16 mmol) was added in a single portion and the reaction allowed to warm to 5-10° C. over 3 h. The reaction was quenched with sat. Na2SO3, diluted with CH2Cl2 and separated. The organics were washed with Na2SO3 and NaHSO3 and dried over MgSO4. After filtration, the organics were concentrated to approximately 20 mL and diluted with an additional 20 mL of hexanes. The title compound was isolated as a tan precipitate by filtration.
Reaction SMILES: [CH2:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][O:3][C:2]1=[O:12].[BrH:13].C(O)(=O)C>O>[Br:13][CH2:4][CH2:5][C:6]1([CH2:1][C:2]([OH:3])=[O:12])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: Br
Reactant: O=C1CC2(CCCCC2)CCO1
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)CC1(CCBr)CCCCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To 3-oxaspiro[5.5]undecan-2-one (16.9 g)was added a 30% hydrogen bromide/acetic acid solution (75 mL). The reaction solution was stirred at room temperature for 48 hours. Water was added to the solution, and the crystals thus separated were recovered by filtration and washed with water. The resulting crystals were dissolved in ethyl acetate, and the solution was dried over anhydrous magnesium sulfate and filtered. The filtrate was then concentrated under reduced pressure to give crude crystals. The crude crystals thus obtained were recrystallized from ethyl acetatehexane to give the title compound (20.0 g).
Reaction SMILES: BrC[C:3]1[C:12]([N+:13]([O-:15])=[O:14])=[CH:11][C:10]([Cl:16])=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]>O1CCOCC1.O>[Cl:16][C:10]1[CH:9]=[C:4]2[C:3]([CH2:8][O:7][C:5]2=[O:6])=[C:12]([N+:13]([O-:15])=[O:14])[CH:11]=1
Reactant: COC(=O)c1cc(Cl)cc([N+](=O)[O-])c1CBr
Solvent: O
Solvent: C1COCCO1
Product: O=C1OCc2c1cc(Cl)cc2[N+](=O)[O-]
Yield: 82.1 %

Procedure:
A mixture of methyl 2-(bromomethyl)-5-chloro-3-nitrobenzoate (7 g, 22.8 mmol) in 1,4-dioxane (50 mL) and water (50 mL) was heated to reflux for 4 days. Dioxane was removed under reduced pressure. The residue was extracted with EtOAc (300 mL×4). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give crude product, which was purified by silica gel chromatography (petroleum ether to petroleum ether/EtOAc=5:1) to give the title compound (4 g, yield 82%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:26]=[C:12]2[C:13]([NH:17][C:18]3[CH:23]=[C:22](C)[N:21]=[C:20](C)[N:19]=3)=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1.[Cl:27]C1C2=CN(C3C(Cl)=CC=CC=3Cl)N=C2C=CN=1.NC1C=C(Cl)N=CN=1>>[Cl:27][C:22]1[N:21]=[CH:20][N:19]=[C:18]([NH:17][C:13]2[C:12]3=[CH:26][N:9]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=4[Cl:8])[N:10]=[C:11]3[CH:16]=[CH:15][N:14]=2)[CH:23]=1
Reactant: Cc1cc(Nc2nccc3nn(-c4c(Cl)cccc4Cl)cc23)nc(C)n1
Reactant: Clc1cccc(Cl)c1-n1cc2c(Cl)nccc2n1
Agent: Nc1cc(Cl)ncn1
Product: Clc1cc(Nc2nccc3nn(-c4c(Cl)cccc4Cl)cc23)ncn1
Yield: 57 %

Procedure:
Following the procedure described above for [2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-(2,6-dimethylpyrimidin-4-yl)amine, 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine and 4-amino-6-chloropyrimidine were reacted to afford the title compound as a yellow solid (244 mg, 57% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.14 (br s, 1H), 9.15 (s, 1H), 8.76 (s, 1H), 8.70 (s, 1H), 8.04 (d, J=6.4 Hz, 1H), 7.81 (d, J=8.1 Hz, 2H), 7.71 (t, J=8.1 Hz, 1H), 7.30 (d, J=6.4 Hz, 1H). LCMS (Method D): RT=2.40 min, m/z: 391 [M+H+].
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][CH2:7][N:8]([S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[CH:23][CH:22]=1)(=[O:20])=[O:19])[C:9]1([C:15](O)=[O:16])[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:5])[CH3:2].C(Cl)(=O)C([Cl:38])=O.CN(C)C=O>ClCCl>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][CH2:7][N:8]([C:9]1([C:15]([Cl:38])=[O:16])[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCOC(=O)CCN(C1(C(=O)O)CCOCC1)S(=O)(=O)c1ccc(Oc2ccc(F)cc2)cc1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCOC(=O)CCN(C1(C(=O)Cl)CCOCC1)S(=O)(=O)c1ccc(Oc2ccc(F)cc2)cc1
Reaction time: 8 h

Procedure:
A solution of (15.1 mmol) of the product from Step E in 73 mL of dichloromethane is treated with 1.4 mL (17 mmol, 1.1 equivalents) of oxalyl chloride and 0.02 mL (0.3 mmol, 0.02 equivalents) of dimethylformamide at ambient temperature, causing some bubbling, and is stirred overnight. The resulting solution of the title compound is used in step G without isolation.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:17]([O:19]CC)=[O:18])=[N:4][O:5][C:6]=1[C:7]1[CH2:16][CH2:15][C:10]2([CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:9][CH:8]=1.[OH-].[Na+].Cl>C(O)C.O>[CH3:1][C:2]1[C:3]([C:17]([OH:19])=[O:18])=[N:4][O:5][C:6]=1[C:7]1[CH2:16][CH2:15][C:10]2([CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:9][CH:8]=1
Reactant: CCOC(=O)c1noc(C2=CCC3(CCCC3)CC2)c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1c(C(=O)O)noc1C1=CCC2(CCCC2)CC1
Temperature: 25 °C

Procedure:
To a stirred solution of ethyl 4-methyl-5-(spiro[4.5]dec-7-en-8-yl)isoxazole-3-carboxylate (180 mg, 0.622 mmol) in ethanol (10 mL), 2M NaOH (aq) (0.311 mL, 0.622 mmol) was added and the reaction mixture was stirred at room temperature. The resulting mixture was diluted with water (30 mL) and acidified to pH 5-6 by the addition of 2M HCl (aq). The aqueous was extracted with EtOAc (2×20 mL) and the combined organic extracts were washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound;
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C@@H:13]([C:17]([O:19][CH3:20])=[O:18])[CH:14]([CH3:16])[CH3:15].CCN(C(C)C)C(C)C>ClCCl>[CH3:20][O:19][C:17](=[O:18])[CH:13]([NH:12][S:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9])[CH:14]([CH3:16])[CH3:15]
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1
Reactant: COC(=O)[C@H](N)C(C)C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C(NS(=O)(=O)c1ccc(Br)cc1)C(C)C
Temperature: 0 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
Step 1A [Intermediate 1] To a dry round-bottom flask was added 4-Bromo-benzenesulfonyl chloride (12.2 g, 47.7 mmol, 1 equiv.), anhydrous methylene chloride (170 mL), and H-D-Val-OMe (8.0 g, 47.7 mmol, 1 equiv.). The mixture was cooled to 0° C. in an ice bath followed by the addition of Hunig base (19.11 mL, 109.7 mmol, 2.3 equiv.). The reaction mixture was allowed to warm to room temperature and was stirred overnight. Reaction was complete as determined by TLC. The reaction mixture was then diluted with dichloromethane (100 mL) and washed with brine. The organic layer was dried over anhydrous MgSO4, solvent evaporated to yield 2-(4-Bromo-benzenesulfonylamino)-3-methyl-butyric acid methyl ester in 96% yield (16.0 g). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.87 (d, J=6.82 Hz, 3 H) 0.96 (d, J=6.82 Hz, 3 H) 2.04 (m, 1 H) 3.49 (s, 3 H) 3.74 (d, J=14.40 Hz, 1 H) 5.10 (d, J=9.85 Hz, 1 H) 7.66 (m, 4 H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:20])=[C:7]([C:16]([O:18]C)=O)[C:8]([C:12]([O:14]C)=O)=[N:9]2)=[CH:4][CH:3]=1.Cl.[CH3:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][NH2:30])=[CH:25][CH:24]=1.C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[O:20])[C:7]3[C:16]([OH:18])=[N:30][N:29]([C:26]4[CH:27]=[CH:28][C:23]([CH3:22])=[CH:24][CH:25]=4)[C:12](=[O:14])[C:8]=3[NH:9][C:10]=2[CH:11]=1
Reactant: Cc1ccc(NN)cc1
Reactant: COC(=O)c1nc2cc(Cl)ccc2c(O)c1C(=O)OC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: Cc1ccc(-n2nc(O)c3c(=O)c4ccc(Cl)cc4[nH]c3c2=O)cc1
Temperature: 25 °C
Yield: 49.3 %

Procedure:
To a stirred suspension of dimethyl 7-chloro-4-hydroxyquinoline-2,3-dicarboxylate (3.90 g, 13.3 mM) and 4-methylphenyl hydrazine hydrochloride (14.8 g, 93.2 mM) in ethanol (140 mL) was added triethylamine (14.8 mL, 106.4 mM). The resulting brown solution was refluxed for 16 hours during which time a precipitate formed. The resulting suspension was cooled to room temperature and filtered to give the 4-methylphenyl hydrazine salt of the title compound as a grey powder (2.30 g). This material was refluxed in glacial acetic acid (45 mL) for 2 hours and cooled to room temperature. The resulting brown suspension was filtered to give the title compound (1.60 g, 34%) as a tan powder, mp 380-382° C.; MS(CI): 354 (M+H).
Reaction SMILES: [NH2:1][C:2]([CH2:21][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])([CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:3][CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].C(N(CC)CC)C.[C:37](Cl)(=[O:39])[CH3:38]>C(Cl)Cl>[C:26]([O:25][C:23](=[O:24])[CH2:22][CH2:21][C:2]([NH:1][C:37](=[O:39])[CH3:38])([CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:3][CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:9])[CH3:10])=[O:6])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)(C)OC(=O)CCC(N)(CCC(=O)OC(C)(C)C)CCC(=O)OC(C)(C)C
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)NC(CCC(=O)OC(C)(C)C)(CCC(=O)OC(C)(C)C)CCC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 4 h
Yield: 71.9 %

Procedure:
To 5 ml CH2Cl2 was added 1 g of triester 62 (2.4 mmol, 1 equiv) and 0.3 g triethylamine (2.9 mmol, 1.2 equiv.) The solution was cooled to 0° C. with an ice bath and 0.23 g acetyl chloride (2.9 mmol, 1.2 equiv) was added dropwise. The solution was stirred for a further 4 hours and allowed to warm slowly to room temperature. The solution was poured into a separating funnel and washed with 2×15 ml HCl (5% aqueous) and 1×15 ml concentrated NaCl. The solution was dried over Na2SO4 and the solvent was removed in vacuo. The residue was dissolved in minimal EtOAc and loaded onto a silica column, where it was purified by column chromatography with EtOAc and hexane (1:1) to give 0.79 g of a white solid in 72% yield.
Reaction SMILES: [CH3:1][N:2]1[C:12]2[C:7](=[C:8]([C:15](=[O:18])[CH2:16]Cl)[CH:9]=[CH:10][C:11]=2[O:13][CH3:14])[CH:6]=[CH:5][C:3]1=[O:4].[CH:19]([NH2:22])([CH3:21])[CH3:20]>C(O)(C)C>[CH3:1][N:2]1[C:12]2[C:7](=[C:8]([C:15](=[O:18])[CH2:16][NH:22][CH:19]([CH3:21])[CH3:20])[CH:9]=[CH:10][C:11]=2[O:13][CH3:14])[CH:6]=[CH:5][C:3]1=[O:4]
Reactant: COc1ccc(C(=O)CCl)c2ccc(=O)n(C)c12
Reactant: CC(C)N
Solvent: CC(C)O
Product: COc1ccc(C(=O)CNC(C)C)c2ccc(=O)n(C)c12
Yield: 13.7 %

Procedure:
2.7 g of 1-methyl-5-chloroacetyl-8-methoxycarbostyril (IV) prepared as described in Example 1 was dissolved in 40 ml of isopropanol, and 9 g of isopropylamine (III) was added to the solution while heating the solution at a temperature of 55° to 60° C. over a period of 1.5 hours. After completion of the addition, the mixture was allowed to react for one hour while stirring. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in 40 ml of isopropanol. The solution was then filtered to remove any insoluble material, and the filtrate was adjusted to a pH of 2-3 with concentrated hydrochloric acid. The mixture was cooled with ice and the precipitate formed was filtered and recrystallized from ethanol to obtain 0.4 g of white amorphous 1-methyl-5-isopropylaminoacetyl-8-methoxycarbostyril (IIb) hydrochloride. The product thus obtained was confirmed by elemental analysis and IR spectral analysis.
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[NH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[N:14][C:15]([O:21][CH3:22])=[CH:16][CH:17]=2)[N:12]=1>C(O)CC>[CH3:22][O:21][C:15]1[N:14]=[C:13]2[C:18]([CH:19]=[CH:20][C:11]([NH:10][C:1]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=3)=[O:9])=[N:12]2)=[CH:17][CH:16]=1
Reactant: O=C(O)c1cccnc1
Reactant: COc1ccc2ccc(N)nc2n1
Solvent: CCCO
Product: COc1ccc2ccc(NC(=O)c3cccnc3)nc2n1
Temperature: 4 °C
Yield: 77.7 %

Procedure:
The prccedure is similar to that described in Example 1, but starting with nicotinic acid (7.4 g), N,N'-carbonyldiimidazole (9.7 g) and 2-amino-7-methoxy-1,8-naphthyridine (7 g). After filtration, washing with water and drying, the crystallised solid formed during the reaction (10.3 g; m.p. 245° C.) is dissolved in boiling 1-propanol (900 cc). After being cooled for 3 hours at 4° C., the crystallised solid is separated by filtration, washed with 1-propanol (3×20 cc) and dried at 50° C. under reduced pressure (0.067 kPa). N-(7-methoxy-1,8-naphthyridin-2-yl)-3-pyridylcarboxamide (8.7 g) is produced, m.p. 247° C.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][NH2:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:10]([O:12][C:13]([C:15]1[C:16](=[O:38])[C:17]2[CH:22]=[N:21][C:20](S(C)(=O)=O)=[N:19][C:18]=2[N:27]([C:29]2[CH:30]=[C:31]3[C:35](=[CH:36][CH:37]=2)[CH2:34][CH2:33][CH2:32]3)[CH:28]=1)=[O:14])[CH3:11]>>[CH2:10]([O:12][C:13]([C:15]1[C:16](=[O:38])[C:17]2[CH:22]=[N:21][C:20]([NH:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[N:19][C:18]=2[N:27]([C:29]2[CH:30]=[C:31]3[C:35](=[CH:36][CH:37]=2)[CH2:34][CH2:33][CH2:32]3)[CH:28]=1)=[O:14])[CH3:11]
Reactant: NCCN1CCOCC1
Reactant: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(S(C)(=O)=O)ncc2c1=O
Product: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(NCCN3CCOCC3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 1(Step F) the title compound was prepared from 2-morpholin-4-yl-ethylamine (4.8 μL, 0.036 mmol) and 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (from Example 1(Step E), 15 mg, 0.036 mmol). 15.5 mg of 8-indan-5-yl-2-(2-morpholin-4-yl-ethylamino)-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.24 (s, 1H), 8.45 (s, 1H), 7.34 (d, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 6.19 (br, 1H), 4.36 (q, 2H), 3.65 (m, 4H), 3.24 (m, 2H), 2.99 (m, 4H), 2.30-2.60 (m, 6H), 2.17 (m, 2H), 1.37 (t, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C25H29N5O4: 464.22 (M+H). Found: 464.4.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:26]([O-])=O)=[C:6]([CH:25]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)(=[O:18])=[O:17])=[CH:12][CH:11]=1)=[O:8].S(S([O-])=O)([O-])=O.[Na+].[Na+]>O1CCCC1.CO.O>[NH2:26][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:25][C:6]=1[C:7]([NH:9][C:10]1[CH:11]=[CH:12][C:13]([S:16]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)(=[O:18])=[O:17])=[CH:14][CH:15]=1)=[O:8]
Reactant: O=C(Nc1ccc(S(=O)(=O)N2CCOCC2)cc1)c1cc(Cl)ccc1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc(Cl)cc1C(=O)Nc1ccc(S(=O)(=O)N2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
11.10 g (26.1 mmol) of 5-chloro-N-(4-(morpholine-4-sulfonyl)-phenyl)-2-nitro-benzamide were dissolved in 440 ml of tetrahydrofuran/methanol (1:1) and a solution of 27.23 g (156.4 mmol) of sodium dithionite in 330 ml of water was added dropwise. After stirring for 1 h at room temperature the organic solvents were removed in rotary evaporator, and the precipitated product was filtered off with suction and purified by chromatography over silica with methylene chloride/methanol (9:1). 5.68 g (55%) of the title compound having a melting point of 229-231° C. were obtained.
Reaction SMILES: [C:1]1([CH2:7][C:8]([O:10][CH3:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:12](Br)([CH3:14])[CH3:13].S([C:20]1[CH:26]=CC(C)=C[CH:21]=1)([O-])(=O)=O.C[N+](C)(C)C.[Cl-].[NH4+]>CN(C)C=O>[CH:12]([CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]([O:10][CH3:11])=[O:9])([CH3:14])[CH3:13].[CH:20]([CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]([OH:10])=[O:9])([CH3:26])[CH3:21]
Reactant: COC(=O)Cc1ccccc1
Reactant: CC(C)Br
Reactant: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: C[N+](C)(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CC(C)C(C(=O)O)c1ccccc1
Product: COC(=O)C(c1ccccc1)C(C)C

Procedure:
Into the cathode chamber of an electrolytic cell divided with a diaphragm (asbestos) was placed a solution of 10 mmols of methyl phenylacetate, 12 mmols of isopropyl bromide and 1.0 g of tetramethylammonium tosylate in 30 ml of anhydrous dimethylformamide. Constant current electrolysis was conducted at 0.2 A/cm2 with use of lead for the anode and carbon for the cathode. After passing 1.5 F of electricity per mol of the methyl phenylacetate at 20° to 25° C., the cathode solution was added to a saturated aqueous solution of ammonium chloride and the mixture was extracted twice with ether. The ether was distilled off and the residue was purified by silica gel column chromatography using hexane-ethyl acetate (10:1), giving methyl α-isopropylphenylacetate in a yield of 80% and α-isopropylphenylacetic acid in a yield of 9%. The spectral data of the ester were as follows.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:3]=1.Cl.[CH2:25]([NH:29][C:30]([CH:32]1[CH2:37][CH2:36][CH2:35][NH:34][CH2:33]1)=[O:31])[CH:26]([CH3:28])[CH3:27].C(N(CC)CC)C.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C=O)C>[CH2:25]([NH:29][C:30]([CH:32]1[CH2:37][CH2:36][CH2:35][N:34]([C:2]2[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)[N:3]=2)[CH2:33]1)=[O:31])[CH:26]([CH3:28])[CH3:27]
Reactant: CC(C)CNC(=O)C1CCCNC1
Reactant: CCCC(C(=O)OC)c1c(C)nc(Cl)nc1-c1ccc(C)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCC(C(=O)OC)c1c(C)nc(N2CCCC(C(=O)NCC(C)C)C2)nc1-c1ccc(C)cc1
Temperature: 110 °C

Procedure:
A mixture of methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate (0.100 g; 0.300 mmol), N-isobutylpiperidine-3-carboxamide hydrochloride (0.198 g; 0.901 mmol) and triethylamine (0.211 mL; 1.50 mmol) in a mixture of tetrahydrofuran (2 mL) and DMF (0.4 mL) was heated at 110° C. in a sealed tube for 18 h. After cooling, the reaction mixture was diluted in a saturated solution of sodium hydrogen carbonate and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-40%) in heptane (with 0.5% of triethyl amine) furnished 0.150 g (quantitative) of the title compound as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](F)=[CH:6][CH:5]=1)([O-:3])=[O:2].O.[CH2:12]([NH2:16])[CH:13]([NH2:15])[CH3:14]>>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:16][CH2:12][CH:13]([NH2:15])[CH3:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(N)CN
Reactant: O=[N+]([O-])c1ccc(F)cc1
Solvent: O
Product: CC(N)CNc1ccc([N+](=O)[O-])cc1
Reaction time: 1 h
Yield: 92.9 %

Procedure:
2.8 g of 4-nitrofluorobenzene were heated to 80° C. in 29.6 g of propylenediamine and then stirred for 1 hour at the same temperature. The reaction mixture was poured into water and precipitated crystals were collected by filtration, thereby obtaining 3.6 g of N-(4-nitrophenyl)propylenediamine as crystals.
Reaction SMILES: [CH2:1]1COCC1.[C:6]1([CH:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CCN(CC)CC>C1(C)C=CC=CC=1>[C:6]1([CH:12]2[CH2:17][CH2:16][C:15](=[CH2:1])[CH2:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C1CCC(c2ccccc2)CC1
Reactant: C1CCOC1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: C=C1CCC(c2ccccc2)CC1
Reaction time: 0.17 h
Yield: 10 %

Procedure:
BDAM (2.83 grams) was suspended in 40 milliliters of toluene and 2.2 milliliters of THF were added dropwise. After 10 minutes of stirring, 2.10 grams of 4-phenylcyclohexanone were added. The reaction mixture was refluxed for 1 hour and hydrolyzed with hydrated Ca(OH)2 in the presence of Et3N. After the usual work up, 0.21 grams of 4-phenyl-1-methylenecyclohexane was isolated (10% yield).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH3:16][O:17][C:18]1[CH:19]=[C:20](O)[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2.CCN(CC)CC>ClCCl>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[C:18]([O:17][CH3:16])[CH:19]=1)(=[O:5])=[O:4]
Reactant: COc1cc(O)c2ccccc2c1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(OS(=O)(=O)C(F)(F)F)c2ccccc2c1
Yield: 74.2 %

Procedure:
Trifluoromethanesulfonic anhydride (9.35 g, 32.8 mmol) was added dropwise to a solution of 3-methoxy-1-naphthol (5.77 g, 32.8 mmol) and Et3N (10 ml) in dichloromethane (100 ml) at 0° C. with stirring. After 1 h the resulting solution was washed with HCl (50 ml, 1 M) and saturated Na2CO3 (50 ml), dried (MgSO4) and the solvent removed under reduced pressure. The residue was chromatographed on silica using EtOAc (7% in hexanes) to give the title compound (7.45 g, 74%) as a colourless oil.