Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12])[CH:2]=1.N1C=CC=C(CCCO)C=1>CO.C(Cl)(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[O:12])[CH:2]=1
Reactant: OCCCCCc1cccnc1
Agent: OCCCc1cccnc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: O=CCCCCc1cccnc1
Yield: 96 %

Procedure:
Utilising the procedure described in example 10(a) employing 5-(3-pyridyl)-1-pentanol in lieu of 3-(3-pyridyl)-1-propanol gave after purification by column chromatography (flash silica gel, 5% methanol in chloroform) 5-(3-pyridyl)-1-pentanal (96% yield).
Reaction SMILES: O[C:2]1C(C)=C2C(=CC=1C)NCC2C.[C:14]([N:19]1[C:27]2[C:22](=[C:23]([CH3:30])[C:24]([OH:29])=[C:25]([CH3:28])[CH:26]=2)[CH:21]([CH3:31])[CH2:20]1)(=[O:18])[CH:15]([CH3:17])[CH3:16].C(Cl)(=O)C(C)C>>[C:14]([N:19]1[C:27]2[C:22](=[C:23]([CH3:30])[C:24]([OH:29])=[C:25]([CH3:28])[CH:26]=2)[CH:21]([CH3:31])[CH2:20]1)(=[O:18])[C:15]([CH3:2])([CH3:17])[CH3:16]
Reactant: Cc1cc2c(c(C)c1O)C(C)CN2C(=O)C(C)C
Reactant: Cc1cc2c(c(C)c1O)C(C)CN2
Agent: CC(C)C(=O)Cl
Product: Cc1cc2c(c(C)c1O)C(C)CN2C(=O)C(C)(C)C
Yield: 75 %

Procedure:
Treatment of indoline 10 (160 mg, 0.9 mmoI) according to a procedure similar to one used for preparing 11b, with substitution of pivaloyl chloride for isobutyryl chloride, afforded 11c (176 mg, 75% yield) as a colorless solid, mp 144°-145° C. Spectral data: 13C NMR: δ 11.7, 16.4, 19.5, 27.6, 39.9, 57.4, 117.9, 119.2, 121.9, 133.7, 136.0, 148.8, 176.0; HRMS: calcd. for C16H23NO2 261.1229, fnd. 261.1921. Anal: calcd. for C16H23NO2C, 73.53, H, 8.87, N, 5.36, fnd. C, 73.60, H, 8.91, N, 5.36.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][N:11]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])[CH:5]=[CH:6][CH:7]=1.[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[CH2:28]O>>[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[CH2:28][O:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][N:11]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1cccc(O)c1
Reactant: OCC1CCCCO1
Product: O=C1c2ccccc2C(=O)N1CCCc1cccc(OCC2CCCCO2)c1

Procedure:
Mitsunobu reaction of phenol 58 with (tetrahydro-2H-pyran-2-yl)methanol gave 2-(3-(3-((tetrahydro-2H-pyran-2-yl)methoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.2 g, 18%): 1H NMR (400 MHz, CDCl3) δ 7.81-7.84 (m, 2H), 7.69-7.72 (m, 2H), 7.12-7.16 (m, 1H), 6.76-6.79 (m, 2H), 6.81 (s, 1H), 6.69 (d, J=8.8 Hz, 1H), 4.17 (d, J=6.2 Hz, 2H), 3.76 (t, J=7.2 Hz, 2H), 3.60-3.66 (m, 1H), 3.44-3.52 (m, 2H), 2.69 (t, J=8.0 Hz, 2H), 1.98-2.06 (m, 2H), 1.86-1.92 (m, 2H), 1.60-1.72 (m, 2H), 1.24-1.40 (m, 2H).
Reaction SMILES: [OH:1][C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[Br:12]Br>O>[Br:12][C:5]1[N:4]=[C:3]([C:8]([O:10][CH3:11])=[O:9])[C:2]([OH:1])=[CH:7][CH:6]=1
Reactant: BrBr
Reactant: COC(=O)c1ncccc1O
Solvent: O
Product: COC(=O)c1nc(Br)ccc1O
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.7 %

Procedure:
A stirred solution of methyl 3-hydroxy-2-pyridinecarboxylate (1.69 g, 11.0 mmol) in water (75 mL) at ambient temperature was treated dropwise with bromine (2.39 g, 15.0 mmol). The reaction mixture was stirred at ambient temperature for 3 h, during which time a fine white precipitate formed. The mixture was extracted with CH2Cl2 (100 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to give 2.11 g (82%) of methyl 6-bromo-3-hydroxy-2-pyridinecarboxylate as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 10.69 (s, 1H), 7.55 (d, 1H, J=8.8 Hz), 7.27 (d, 1H, J=8.8 Hz), 4.04 (s, 3H); LRMS (APCI), m/z 232/234 (M+H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][C:3]=1[NH2:16].[CH3:17][C:18]1([CH3:27])[CH2:23][CH2:22][C:21](B(O)O)=[CH:20][CH2:19]1>>[CH3:17][C:18]1([CH3:27])[CH2:23][CH2:22][C:21]([C:2]2[CH:7]=[C:6]([CH2:8][CH2:9][N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH:5]=[CH:4][C:3]=2[NH2:16])=[CH:20][CH2:19]1
Reactant: CC1(C)CC=C(B(O)O)CC1
Reactant: Nc1ccc(CCN2CCOCC2)cc1Br
Product: CC1(C)CC=C(c2cc(CCN3CCOCC3)ccc2N)CC1

Procedure:
The title compound was prepared by Suzuki coupling of 2-bromo-4-(2-morpholin-4-yl-ethyl)-phenylamine (as prepared in Example 33, step (b)) and 4,4-dimethyl-1-cyclohexen-1-ylboronic acid according to the procedure in Example 1, step (e). Mass spectrum (ESI, m/z): Calcd. for C20H30N2O, 315.2 (M+H). found 315.1.
Reaction SMILES: [Br:1][C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]=O)=[CH:18][CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH2:24](P(=O)(OCC)OCC)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CS(C)=O.CC(C)([O-])C.[K+]>O>[Br:1][C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]=[CH:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:18][CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2
Reactant: O=Cc1ccc(-c2c3ccccc3c(Br)c3ccccc23)cc1
Reactant: CCOP(=O)(Cc1ccccc1)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: Brc1c2ccccc2c(-c2ccc(C=Cc3ccccc3)cc2)c2ccccc12
Temperature: 25 °C
Reaction time: 10 h
Yield: 85.6 %

Procedure:
Under an atmosphere of argon, 9-bromo-10-(4-formylphenyl)-anthracene (3.9 g, 11 mmole) and diethyl benzylphosphonate (3 g, 13 mmole, 1.2 eq) were suspended into DMSO (25 ml). To the resultant suspension, potassium t-butoxide (1.6 g, 14 mmole, 1.1 eq) was added and the obtained mixture was stirred at the room temperature for 10 hours and left standing for one night. The reaction mixture was diluted with water (50 ml) and subjected to extraction with toluene (300 ml). The organic layer was washed with water (50 ml) and a saturated aqueous solution of sodium chloride (50 ml) and dried with magnesium sulfate. Then, the solvent was removed by distillation and a yellow solid was obtained. The obtained solid was purified by recrystallization from toluene (40 ml) and yellow needle crystals (4.1 g, 86%) were obtained.
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([CH2:9]Br)=[CH:7][N:6]=[C:5]([Cl:11])[CH:4]=1.[CH3:12][Si:13]([CH3:29])([CH3:28])[CH2:14][CH2:15][O:16][CH2:17][N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH2:20][C:19]1=[O:27].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:11][C:5]1[N:6]=[CH:7][C:8]2[CH2:9][C:20]3([CH2:2][C:3]=2[CH:4]=1)[C:21]1[C:22](=[N:23][CH:24]=[CH:25][CH:26]=1)[N:18]([CH2:17][O:16][CH2:15][CH2:14][Si:13]([CH3:28])([CH3:12])[CH3:29])[C:19]3=[O:27]
Reactant: Clc1cc(CBr)c(CBr)cn1
Reactant: C[Si](C)(C)CCOCN1C(=O)Cc2cccnc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCN1C(=O)C2(Cc3cnc(Cl)cc3C2)c2cccnc21
Reaction time: 21 h

Procedure:
To a solution of 4,5-bis(bromomethyl)-2-chloropyridine from Step D (254 mg, 0.85 mmol) and 1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (226 mg, 0.86 mmol, described in Intermediate 4) in DMF (8 mL) was added cesium carbonate (455 mg, 1.40 mmol). After 21 h, the reaction mixture was poured into H2O (60 mL) and extracted with EtOAc (2×60 mL). The organic layer was washed with brine (40 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—100:0 to 0:100, to give the title compound. MS: m/z=402 (M+1).
Reaction SMILES: [C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)=[CH:10][C:9]([CH2:19][CH2:20][CH:21]=O)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:27]=[CH:28][C:29]=1[CH3:30].CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[CH3:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:32][CH2:33][N:34]([CH2:21][CH2:20][CH2:19][C:9]3[CH:10]=[C:11]([C:12]4[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=4)[N:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[N:8]=3)[CH2:35][CH2:36]2)[CH:27]=[CH:28][C:29]=1[CH3:30]
Reactant: Cc1ccc(-c2cc(CCC=O)nn2-c2ccccc2)cc1
Reactant: Cc1ccc(N2CCNCC2)cc1C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-c2cc(CCCN3CCN(c4ccc(C)c(C)c4)CC3)nn2-c2ccccc2)cc1

Procedure:
118 mg (85%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-phenyl-5-p-tolyl-1H-pyrazol-3-yl)propanal (80 mg, 0.276 mmol), 1-(3,4-dimethylphenyl)piperazine (53 mg, 0.276 mmol), DIPEA (0.072 mL, 0.414 mmol) and NaBH(OAc)3 (175 mg, 0.828 mmol).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].[H-].[Na+].Br[C:12]1([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13]1.O>CN(C)C(=O)C>[N+:1]([C:4]1[CH:5]=[N:6][N:7]([C:12]2([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13]2)[CH:8]=1)([O-:3])=[O:2]
Reactant: CCOC(=O)C1(Br)CCC1
Reactant: O=[N+]([O-])c1cn[nH]c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CCOC(=O)C1(n2cc([N+](=O)[O-])cn2)CCC1
Reaction time: 0.5 h
Yield: 8.1 %

Procedure:
To a solution of 4-nitro-1H-pyrazole (8.2 g) in N,N-dimethylacetamide (70 mL) was added sodium hydride (60% in mineral oil, 3.2 g) in an ice bath, and the mixture was stirred at the same temperature for 30 min. To the reaction mixture was added ethyl 1-bromocyclobutanecarboxylate (15 g) in an ice bath, and the mixture was stirred at room temperature for 10 hr. Water was poured into the reaction mixture, and the reaction mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.4 g).
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([NH2:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[CH2:14]([NH:20][C@H:10]1[CH2:11][CH2:12][C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][CH2:9]1)[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCCN
Reactant: O=C1CCC(c2ccccc2)CC1
Product: CCCCCCN[C@H]1CC[C@H](c2ccccc2)CC1

Procedure:
from 4-phenylcyclohexanone and hexylamine. Colourless oil. Rf value: 0.25 (alumina, petroleum ether/ethyl acetate 9:1, v:v).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[Cl:11].C(O)(=O)C.C(N)=N.[H][H]>[Ni].CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[Cl:11]
Reactant: [H][H]
Reactant: O=[N+]([O-])c1ccc(Cl)c(Cl)c1
Agent: [Ni]
Agent: N=CN
Solvent: CO
Solvent: CC(=O)O
Product: Nc1ccc(Cl)c(Cl)c1
Reaction time: 1 h

Procedure:
48.0 g of 1,2-dichloro-4-nitrobenzene, 2 g of Raney nickel (60%, aqueous), 1.5 g of formamidine acetate and 120 ml of methanol are introduced in an autoclave equipped with gas introduction stirrer. The air in the autoclave is then displaced by nitrogen and then by hydrogen. The hydrogenation is carried out at a pressure of 12 bar and a temperature of 80° C. The hydrogenation time is 1 hour. 1,2-Dichloro-4-aminobenzene, 99.7% pure (analysed by gas chromatography), is obtained in quantitative yield.
Reaction SMILES: [CH:1]1([C:4]2[C:12]([CH:13]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:14][CH2:15][OH:16])=[CH:11][C:10]3[C:6](=[C:7]([C:28]([NH:30][CH3:31])=[O:29])[N:8]([C:21]4[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[CH3:41][S:42]([O:16][CH2:15][CH2:14][CH:13]([C:12]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]2[C:10]([CH:11]=1)=[N:9][N:8]([C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)[C:7]=2[C:28](=[O:29])[NH:30][CH3:31])[S:17]([CH3:20])(=[O:19])=[O:18])(=[O:44])=[O:43]
Reactant: CS(=O)(=O)Cl
Reactant: CNC(=O)c1c2cc(C3CC3)c(C(CCO)S(C)(=O)=O)cc2nn1-c1ccc(C)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CNC(=O)c1c2cc(C3CC3)c(C(CCOS(C)(=O)=O)S(C)(=O)=O)cc2nn1-c1ccc(C)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
To a solution of compound (viii) (9 mg, 0.02 mmol) in DCM (4 mL) at 0° C. were added DIPEA (30 μL, 0.17 mmol) and methanesulfonyl chloride (6 μL, 0.078 mmol). The reaction was stirred at 0° C. for 1 h, at which time it was diluted with DCM (12 mL) and saturated aqueous sodium bicarbonate (4 mL). The aqueous layer was separated and extracted with DCM (12 mL). The combined organic layers were washed with water (5 mL), dried (MgSO4) and evaporated to dryness. The residue was purified by flash column chromatography eluting with EtOAc/heptane (50-100%) to afford racemic 3-[5-cyclopropyl-3-(methylcarbamoyl)-2-(4-methylphenyl)-2H-indazol-6-yl]-3-(methylsulfonyl)propyl methanesulfonate (ix) as a white solid (8 mg, 69%).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][N:8]=1.[Li][CH2:15]CCC.CI.[NH4+].[Cl-]>CCOCC>[Cl:13][C:11]1[CH:10]=[CH:9][N:8]=[C:7]([C:6]2[CH:5]=[CH:4][S:3][C:2]=2[CH3:15])[CH:12]=1
Reactant: Clc1ccnc(-c2ccsc2Br)c1
Reactant: [Li]CCCC
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: CI
Product: Cc1sccc1-c1cc(Cl)ccn1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a solution of 2-(2-bromo-thiophen-3-yl)-4-chloro-pyridine (80 mg, 0.3 mmol) in Et2O (3 mL) at −78° C. was added n-BuLi (1.6 M in hexanes, 0.2 mL). After 10 min, MeI (70 mg, 0.5 mmol) was added. The resulting mixture was maintained at −78° C. for 2 h, then was warmed to room temperature and stirred for 3 h. The reaction mixture was treated with 2 M aqueous NH4Cl and extracted with EtOAc. The organic layer was dried and concentrated to yield a residue. The residue was purified by preparative TLC (hexanes/EtOAc) to yield 4-chloro-2-(2-methyl-thiophen-3-yl)-pyridine as a solid.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.[F:10][C:11]1[CH:12]=[C:13]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]1[C:18]([C:24]#[C:25][CH2:26][N:27]([CH3:29])[CH3:28])=[C:17]3[NH:30][C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][C:36]=4[C:16]3=[CH:15][C:14]2=1>>[F:37][C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:17]1[C:18]([CH2:24][CH2:25][CH2:26][N:27]([CH3:29])[CH3:28])=[C:19]3[NH:20][C:21]4[CH:22]=[CH:23][C:11]([F:10])=[CH:12][C:13]=4[C:14]3=[CH:15][C:16]2=1
Reactant: CN(C)CC#Cc1c2[nH]c3ccc(F)cc3c2cc2c1[nH]c1ccc(F)cc12
Agent: c1ccc2[nH]ccc2c1
Product: CN(C)CCCc1c2[nH]c3ccc(F)cc3c2cc2c1[nH]c1ccc(F)cc12

Procedure:
The title compound was prepared in a manner analogous to Example 144 except the starting indole is 3-(2,10-difluoro-5,7-dihydroindolo[2,3-b]carbazol-6-yl)-N,N-dimethylprop-2-yn-1-amine 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.13 (br s, 2H), 8.67 (s, 1H), 7.88 (dd, J=9.2, 2.4 Hz, 2H), 7.44 (dd, J=8.8, 4.4 Hz, 2H), 7.15 (td, J=9.2, 2.4 Hz, 2H), 3.15 (t, J=5.2 Hz, 2H), 2.29 (t, J=7.2 Hz, 2H), 2.18 (s, 6H), 1.94-1.83 (m, 2H); MS (ESI) m/z 376.3 (M−H)−; MS (ESI) m/z 378.1 (M+H)+
Reaction SMILES: Cl.[C:2]([CH2:4][CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)#[N:3].[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:28])Br.C(=O)([O-])[O-].[K+].[K+].O>CC(C)=O>[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:28])[N:10]1[CH2:9][CH2:8][CH:7]([CH2:6][CH2:5][CH2:4][C:2]#[N:3])[CH2:12][CH2:11]1
Reactant: N#CCCCC1CCNCC1
Reactant: Clc1ccccc1C(Br)c1ccccc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: N#CCCCC1CCN(C(c2ccccc2Cl)c2ccccc2Cl)CC1

Procedure:
20 g (106 mmol) 4-(3-cyanoprop-1-yl)-piperidin hydrochloride, 40.2 g (127 mmol) bis(2-chlorophenyl)-bromomethane and 35.2 g (254 mmol) potassium carbonate are heated to boiling in 90 ml acetone for six hours. After cooling, the mixture is freed from solution under vacuum. The residue is dispersed between 90 ml tolueneand 90 ml water. The aqueous phase is extracted with 10 ml tolueneand the combined organic phases are washed with 10 ml water. The organic phase is concentrated and the residue is chromatographically purified over silica gel with CHCL3. Yield: 11.2 g (27%).
Reaction SMILES: [O:1]([CH2:9][CH2:10][CH:11]1[C:16](=[O:17])[NH:15][C:14]2[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=[CH:21][C:13]=2[O:12]1)[Si](C(C)(C)C)(C)C.[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28]Br.CCO.O.[K+].[Br-]>O>[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28][N:15]1[C:14]2[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=[CH:21][C:13]=2[O:12][CH:11]([CH2:10][CH2:9][OH:1])[C:16]1=[O:17]
Reactant: COc1ccc2c(c1)NC(=O)C(CCO[Si](C)(C)C(C)(C)C)O2
Reactant: Clc1cccc(CBr)c1
Agent: [Br-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: COc1ccc2c(c1)N(Cc1cccc(Cl)c1)C(=O)C(CCO)O2

Procedure:
Prepared from 2-(2-tert-butyldimethylsiloxyethyl)-3,4-dihydro-6-methoxy-3-oxo-2H-1,4-benzoxazine by methods F and G, alkylating with 3-chlorobenzyl bromide, in 80% overall yield. Isolated by crystallization from EtOH/water to afford a white powder, MS (Cl) 348 (MH+); IR (KBr) 3501, 3053, 3021, 2959, 2933, 2876, 2838, 1664, 1618, 1600, 1575, 1512, 1466, 1445, 1435, 1390, 1361, 1337, 1313, 1272, 1237, 1201, 1173, 1107, 1078, 1049, 1030 cm-1 ; 1H NMR (CDCl3) δ 7.27-7.20 (m, 3H), 7.13 (m, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.52 (dd, J=9.1, 2.7 Hz, 1H), 6.41 (d, J=2.7 Hz, 1H), 5.12 (d, J=16.2 Hz, 1H), 4.79 (dd, J=8.2, 5.4 Hz, 1H), 3.92 (m, 2H), 3.68 (s, 3H), 3.39-2.16 (m, 2H), 2.17 (t, J=5.9 Hz, 1H). Anal. Calc'd for C18H18ClNO4.0.25 H2O: C 61.37, H 5.29, N 3.98. Found: C 61.35, H 5.14, N 3.95.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21](O)=[O:22])=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH:47]([CH:50]1[CH2:54][CH2:53][CH2:52][NH:51]1)([CH3:49])[CH3:48].C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([N:51]2[CH2:52][CH2:53][CH2:54][CH:50]2[CH:47]([CH3:49])[CH3:48])=[O:22])=[CH:15]3)=[O:11])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)O)cc3c2)CC1
Reactant: CC(C)C1CCCN1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)C1CCCN1C(=O)c1cc2cc(C(=O)N3CCN(C(C)C)CC3)ccc2[nH]1

Procedure:
The title compound was synthesized in analogy to example 1, from 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid 1:1 hydrochloride, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (commercially available), 2-isopropylpyrrolidine (commercially available) and N,N-diisopropylethylamine in N,N-dimethylformamide to give the desired product after purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile/water/formic acid.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[CH:6](=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[C:7]1([CH:6]([OH:13])[C@@H:2]([C:3]([OH:5])=[O:4])[NH2:1])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=Cc1ccccc1
Reactant: NCC(=O)O
Product: N[C@H](C(=O)O)C(O)c1ccccc1

Procedure:
β-Phenylserine was synthesized from glycine and benzaldehyde in the same way as in Example 1 except that the organic solvent was changed as shown in Table 1. The results are shown in Table 1.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH2:4]O.S(Cl)(Cl)=O.[CH3:16][NH:17][CH3:18]>C(Cl)Cl>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[CH2:4][N:17]([CH3:18])[CH3:16]
Reactant: CNC
Reactant: COc1ccc(N)c(CO)c1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: COc1ccc(N)c(CN(C)C)c1

Procedure:
2-Amino-N,N-dimethyl-5-methoxy-benzylamine was prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and dimethylamine analogous to Example 1. Proof of structure by IR-, UV- and NMR-spectra. IR-spectrum (methylenechloride):
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.Cl.C([NH:19][CH:20]([C:22]1([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)[CH2:25][CH2:24][CH2:23]1)[CH3:21])C1C=CC=CC=1.[BH4-].[Na+].Cl>C(O)C.O>[ClH:32].[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:1][NH:19][CH:20]([C:22]2([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=3)[CH2:23][CH2:24][CH2:25]2)[CH3:21])=[CH:3][CH:4]=1
Reactant: CC(NCc1ccccc1)C1(c2ccc(Cl)c(Cl)c2)CCC1
Reactant: COc1ccc(C=O)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccc(CNC(C)C2(c3ccc(Cl)c(Cl)c3)CCC2)cc1

Procedure:
A stirred mixture of p-anisaldehyde (0.62 ml) and 1-[1-(3,4-dichlorophenyl)cyclobutyl]ethylamine (see Example 1 of published British Patent Specification No. 2098602) in the form of its free base (1.22 g) was heated to 130°-135° for 30 minutes. After cooling the residue was dissolved in ethanol (10 ml) and the solution added to a solution of sodium borohydride (1.5 g) in ethanol (200 ml). The mixture was heated under reflux for one hour. Water (10 ml) and then excess 5N HCl were added and the ethanol removed by evaporation. The residue was basified with aqueous sodium hydroxide solution and an ether extraction performed. The extract was dried and evaporated to give an oil. Hydrogen chloride gas was passed through an ethereal solution of the oil to give N-(4-methoxybenzyl)-1-[1-(3,4-dichlorophenyl)cyclobutyl]ethylamine hydrochloride (m.p. 217°-218° C.).
Reaction SMILES: [F:1][CH:2]([F:24])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]#[CH:13])=[C:7]2[N:6]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:4]=1.Br[C:26]1[CH:27]=[C:28]([S:32]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=1>>[F:24][CH:2]([F:1])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12]#[C:13][C:30]3[CH:31]=[CH:26][CH:27]=[C:28]([S:32]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)(=[O:34])=[O:33])[CH:29]=3)=[C:7]2[N:6]=[C:5]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:4]=1
Reactant: O=S(=O)(c1cccc(Br)c1)N1CCOCC1
Reactant: C#Cc1cnn2c(C(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: O=S(=O)(c1cccc(C#Cc2cnn3c(C(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)c1)N1CCOCC1

Procedure:
The title compound was prepared from 7-difluoromethyl-3-ethynyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.2) (340 mg, 1.0 mmol) and 4-(3-bromo-benzenesulfonyl)-morpholine (example B.31) (275 mg, 1.0 mmol) according to general procedure II. Obtained as a yellow solid (390 mg, 68%). MS (ISP) 563.4 [(M+H)+]; mp 175-176° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.F[C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[N+:23]([O-:25])=[O:24].O>CN(C=O)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:16]2[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=2[N+:23]([O-:25])=[O:24])=[CH:10][CH:9]=1
Reactant: Nc1ccc(F)c([N+](=O)[O-])c1
Reactant: Oc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccc(Oc2ccc(Cl)cc2)c([N+](=O)[O-])c1
Reaction time: 0.5 h

Procedure:
1.4 g of potassium carbonate were added to a solution of 1.29 g of 4-chlorophenol in 8 ml of DMF and, after stirring for 30 minutes, 1.6 g of 4-fluoro-3-nitroaniline were added, and the mixture was stirred at 100° C. for 3 hours. After cooling, 80 ml of water were added and, after brief stirring, the precipitate was filtered off with suction and dried in vacuo at 40° C.