Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1/[CH:8]=[CH:9]/[C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=1[OH:17].[CH:18]([N-:21][CH:22](C)C)(C)[CH3:19].[Li+].CCCCCCC.C1COCC1.O>O1CCCC1>[CH3:22][N:21]1[CH2:18][CH2:19][C@@H:9]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=2[OH:17])[C@@H:8]1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Br:1]
Reactant: Oc1ccc(Cl)cc1/C=C/c1ccccc1Br
Reactant: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCCCCCC
Solvent: O
Solvent: C1CCOC1
Product: CN1CC[C@@H](c2cc(Cl)ccc2O)[C@@H]1c1ccccc1Br
Yield: 79 %

Procedure:
To a solution of trans-2-bromo-5′-chloro-2′-hydroxystilbene (81 g, 261 mmol) in tetrahydrofuran (570 ml) trimethylamine-N-oxide.dihydrate (43.4 g, 390 mmol) was added at ambient temperature. Lithium diisopropylamide in heptane/THF (2M, 1070 ml, 2140 mmol) was then added during the course of 1 hour while maintaining the temperature below 40° C. After completion of the reaction water (120 ml) was added. Solvent was evaporated to a small volume after which ethyl acetate (250 ml) was added. The pH was adjusted to pH 8 with 18% hydrochloric acid (˜250 ml) and ethyl acetate (250 ml) was added. The organic layer was separated and the aqueous layer was again extracted with ethyl acetate (2×120 ml). The combined organic layers were washed with water (325 ml) and with brine, dried (MgSO4) and then evaporated in vacuo. The resulting oil was crystallised from ethanol/water (1/1, v/v) to give the title pyrrolidine (62.0 g, 79%). Purity according to HPLC is 99% a/a.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[S:8][C:9]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:14]=2)=[C:10]([CH3:12])[N:11]=1)=[O:5].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>CC#N>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:15]2[N:14]=[C:13]([C:9]3[S:8][C:7]([NH:6][C:4](=[O:5])[CH2:3][CH2:2][N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[N:11][C:10]=3[CH3:12])[CH:18]=[CH:17][N:16]=2)=[CH:21][CH:22]=1
Reactant: Cc1nc(NC(=O)CCCl)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1
Reactant: C1COCCN1
Solvent: CC#N
Product: Cc1nc(NC(=O)CCN2CCOCC2)sc1-c1ccnc(Nc2ccc(Cl)cc2)n1

Procedure:
By treatment of 3-chloro-N-{5-[2-(4-chloro-phenylamino)-pyrimidin-4-yl]-4-methyl-thiazol-2-yl}-propionamide with morpholine. Anal. RP-HPLC: tR=12.7 min (10-70% MeCN, purity >95%). 1H-NMR (CDCl3) δ: 1.50 (m, 2H, CH2), 2.52 (s, 3H, CH3), 3.05-3.78 (m, 8H, CH2), 3.81 (m, 2H, CH2), 7.12 (d, 1H, J=5.5 Hz, pyrimidinyl-H), 7.30 (d, 2H, J=7.0 Hz, Ph-H), 7.80 (d, 2H, J=7.0 Hz, Ph-H), 8.51 (d, 1H, J=5.0 Hz, pyrimidinyl-H), 9.80 (brs, 1H, NH).
Reaction SMILES: [N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[N:4]([C:10]1[N:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1)[CH2:3][CH2:2]2.[C:17]([C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=1)[C:22]([Cl:24])=[O:23])#[N:18]>>[ClH:24].[N:1]12[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9]1)[N:4]([C:10]1[N:15]=[CH:14][C:13]([NH:16][C:22](=[O:23])[C:21]3[CH:25]=[CH:26][CH:27]=[C:19]([C:17]#[N:18])[CH:20]=3)=[CH:12][CH:11]=1)[CH2:3][CH2:2]2
Reactant: N#Cc1cccc(C(=O)Cl)c1
Reactant: Nc1ccc(N2CCN3CCC2CC3)nc1
Product: Cl
Product: N#Cc1cccc(C(=O)Nc2ccc(N3CCN4CCC3CC4)nc2)c1

Procedure:
Was prepared according to Method G from 6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-ylamine and 3-cyanobenzoyl chloride. Mp. >265° C. (decomp.).
Reaction SMILES: [CH3:1][Li].[C:3]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)(=[O:5])[CH3:4]>C(OCC)C.C1COCC1>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:3]([OH:5])([CH3:1])[CH3:4])[CH:7]=1
Reactant: [Li]C
Reactant: CC(=O)c1cccnc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)(O)c1cccnc1
Yield: 45.9 %

Procedure:
The method followed that of Example 4a, but using methyllithium (1.4 M; 14 ml, 20 mmol) in diethyl ether and 3-acetylpyridine (2.2 ml, 20 mmol) in dry THF (40 ml). Work-up and chromatography, on elution with ether-petrol-triethylamine 30:10:1, afforded the title compound (1.26 g, 46%) as an oil. 1H-NMR (CDCl3) δ1.58 (6H, s, CMe2), 7.22 (1H, m, Py 5-H), 7.85 (1H, m, Py 4-H), 8.32 (1H, m, Py 6-H), 8.65 (1H, m, Py 2-H); MS m/z 137 (M+).
Reaction SMILES: [Mg].II.[CH3:4][CH:5]([CH3:9])[CH2:6][CH2:7]Br.[CH2:10]([Si:16](Cl)([Cl:18])[Cl:17])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>O1CCCC1.CCCCCC>[CH2:10]([Si:16]([CH2:7][CH2:6][CH:5]([CH3:9])[CH3:4])([Cl:18])[Cl:17])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCC[Si](Cl)(Cl)Cl
Reactant: CC(C)CCBr
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCC[Si](Cl)(Cl)CCC(C)C

Procedure:
Anhydrous tetrahydrofuran (125 mL) was put into a reactor with magnesium (5.0 g, 0.21 mol) which had been dehydrated and deaerated, followed by charging of argon gas. A small amount of iodine was slowly added to the mixture. 3-Methylbutylbromide (25 g, 0.17 mol) was added dropwise to the slowly stirred mixture so that the reaction mixture was gradually refluxed. After the reaction was complete, the obtained Grignard reagent was transferred to a dropping funnel. The Grignard reagent was added dropwise to a solution being stirred containing n-hexyltrichlorosilane (38 g, 0.17 mol) in anhydrous tetrahydrofuran (100 mL) in another reactor which had been dehydrated and deaerated, followed by charging of argon gas, at 60° C.-70° C. The reaction mixture was then stirred overnight at room temperature. Hexane (500 mL) was added to the reaction mixture, and the resulting mixture was filtered under pressure, followed by fractional distillation of the filtrate to provide the desired product.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[C:9]([OH:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]#[N:15].[C:16]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:17]=1.C(O)C.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[C:9]([O:12][CH2:16][CH3:17])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]#[N:15]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: N#Cc1cnc2cc(F)c(O)cc2c1Cl
Agent: CCOC(=O)/N=N/C(=O)OCC
Solvent: C1CCOC1
Solvent: CCO
Product: CCOc1cc2c(Cl)c(C#N)cnc2cc1F
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a 0° C. mixture of 4-chloro-7-fluoro-6-hydroxy-3-quinolinecarbonitrile (185 mg, 0.83 mmol), triphenylphosphine (392 mg, 1.49 mmol) and ethanol (153 mg, 3.32 mmol) in 15 mL of tetrahydrofuran is added diethylazodicarboxylate (260 mg, 1.80 mmol). The reaction mixture is kept at 0° C. for 45 minutes then stirred at room temperature overnight. The reaction mixture is concentrated in vacuo and purified by flash column chromatography eluting with a gradient of 1 % ethyl acetate in hexane to 5% ethyl acetate in hexane provides 4-chloro-6-ethoxy-7-fluoro-3-quinolinecarbonitrile, mp 165-166° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([CH3:13])[CH2:11][OH:12])[CH:5]=[CH:6][C:7]=1[F:8].[BH3-]C#N.[Na+].[OH:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:22][C:21]2[CH:20]=[C:19]([OH:18])[CH:26]=[CH:25][CH:24]=2)[CH:10]([CH3:13])[CH2:11][OH:12])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=Cc1cccc(O)c1
Reactant: CC(CO)Nc1ccc(F)c(Cl)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: ClCCCl
Product: CC(CO)N(Cc1cccc(O)c1)c1ccc(F)c(Cl)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
2-[(3-chloro-4-fluorophenyl)amino]propan-1-ol (1-4, 0.030 g, 0.147 mmol) in DCE (1.0 mL) was treated with NaCNBH3 (0.019 g, 0.295 mmol), and 3-hydroxylbenzaldehyde (0.036 g, 0.295 mmol). The resulting mixture stirred at 25° C. for 24 h then concentrated. The reaction was purified by reverse phase liquid chromotography (Semi-prep YMC C-18 Column 5% CH3CN/H2O up to 95% CH3CN/H2O) to give 3-{[(3-chloro-4-fluorophenyl)(2-hydroxy-1-methylethyl)amino]methyl}phenol (1-5). 1H NMR (300 MHz, CDCl3) δ 7.15 (m, 3H), 6.89 (m, 2H), 6.71 (m, 2H), 4.44 (d, J=10.0 Hz, 2H), 4.00 (m, 1H), 3.73 (s, 2H), 1.19 (d, J=6.7 Hz, 3H). MS 310.3 found, 310.7 (M+H+) required.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[C:21]([NH:22][C:23]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[CH:24]=3)=[N:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:33][N:34]([CH3:38])[CH2:35][CH2:36][NH2:37]>CN(C=O)C>[CH3:32][O:31][C:25]1[CH:24]=[C:23]([NH:22][C:21]2[C:12]([NH:11][S:8]([C:5]3[CH:6]=[N:7][C:2]([NH:37][CH2:36][CH2:35][N:34]([CH3:38])[CH3:33])=[CH:3][CH:4]=3)(=[O:10])=[O:9])=[N:13][C:14]3[C:19]([N:20]=2)=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=1
Reactant: CN(C)CCN
Reactant: COc1cc(Nc2nc3ccccc3nc2NS(=O)(=O)c2ccc(Cl)nc2)cc(OC)c1
Solvent: CN(C)C=O
Product: COc1cc(Nc2nc3ccccc3nc2NS(=O)(=O)c2ccc(NCCN(C)C)nc2)cc(OC)c1
Temperature: 130 °C
Reaction time: 8 h
Yield: 19.1 %

Procedure:
6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those used in Example 8, KHCO3 (40 mg, 0.40 mmol), N1,N1-dimethylethane-1,2-diamine (225 μL, 2.0 mmol) and dry DMF (1.0 mL) were combined and heated to 130° C. with stirring overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxy-phenylamino)-quinoxalin-2-yl)-6-(2-(dimethylamino)ethylamino)pyridine-3-sulfonamide (21.0 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ 8.76 (br s, 1H), 8.63 (d, 1H), 8.07 (dd, 1H), 7.40 (m, 1H), 7.34 (m, 1H), 7.28 (d, 2H), 7.14 (m, 4H), 6.47 (d, 1H), 6.12 (m, 1H), 3.75 (s, 6H), 3.35 (m, 2H), 3.14 (m, 2H), 2.74 (s, 6H). MS (EI) m/z for C25H29N7O4S: 524.1 (MH+).