Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([NH:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[C:6]([N+:15]([O-])=O)=[CH:5][CH:4]=1.[CH:18]([C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1)=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:10][CH2:11][CH2:12][O:13][CH3:14])[C:18]([CH:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])[CH2:21]3)=[N:15][C:6]2=[CH:5][CH:4]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](C=O)C1
Reactant: COCCCNc1nc(OC)ccc1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Product: COCCCn1c(C2CCCN(C(=O)OC(C)(C)C)C2)nc2ccc(OC)nc21
Yield: 76 %

Procedure:
6-Methoxy-N-(3-methoxypropyl)-3-nitropyridin-2-amine (33B) (1.56 mmol max, crude oil) and (R)-tert-butyl 3-formylpiperidine-1-carboxylate (1.56 mmol, 0.332 g) were added to an oven dried 50 mL round-bottomed flask equipped with a reflux condenser and for stirring under nitrogen. Ethanol (4 mL) and dimethyl sulfoxide (2 mL) were added and the solution was allowed to stir at room temperature for 5 min. Sodium hydrosulfite (4.68 mmol; 0.959 g of 85%) was then added and the resultant mixture was heated to reflux and allowed to stir for 16 hr. The reaction solution was then concentrated in-vacuo, poured into water (100 mL), extracted with ethyl acetate, and washed once with saturated aqueous sodium chloride. The organic layer was collected and subsequently dried with anhydrous Na2SO4 and filtered. This filtrate was collected, concentrated, and dried in-vacuo affording a brown oil that was further purified by silica gel chromatography (20% CH3CN/CH2Cl2) to afford tert-butyl 3-(5-methoxy-3-(3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidine-1-carboxylate (33C) as a clear oil (1.19 mmol, 0.481 g, 76% yield over 2-steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9H) 1.54-1.70 (m, 1H) 1.84 (dt, J=13.83, 2.81Hz, 1H) 2.02-2.21 (m, 4H) 2.73-2.88 (m, 1H) 2.96-3.18 (m, 2H) 3.29-3.41 (m, 5H) 3.98 (s, 3H) 4.08-4.44 (m, 4H) 6.65 (d, J=8.59 Hz, 1H) 7.86 (d, J=8.59 Hz, 1H). ESI-MS: m/z 405.5 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]([Cl:24])([Cl:23])[Cl:22])=[O:18])[CH2:13][CH:12]2[O:25][CH2:26][C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:28]=2)[CH:8]=[CH:9][CH:10]=1.[N-:37]=[C:38]=[O:39].[Na+]>>[C:38]([O:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]([Cl:22])([Cl:23])[Cl:24])=[O:18])[CH2:13][CH:12]2[O:25][CH2:26][C:27]2[CH:36]=[CH:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:28]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:39])[NH2:37]
Reactant: [N-]=C=O
Reactant: O=C(OCC(Cl)(Cl)Cl)N1CCC(c2cccc(OCCO)c2)C(OCc2ccc3ccccc3c2)C1
Agent: [Na+]
Product: NC(=O)OCCOc1cccc(C2CCN(C(=O)OCC(Cl)(Cl)Cl)CC2OCc2ccc3ccccc3c2)c1

Procedure:
In an analogous manner to that described in Example 24(m), by reacting 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate with sodium isocyanate there was obtained 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-carbamoyloxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless solid; Rf : 0.40 (SiO2, methylene chloride:methanol=9:1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:10])[CH:9]=1)[CH2:5]Br.C1N2CN3CN(C2)CN1C3.Cl.[OH2:22]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:10])[CH:9]=1)[CH:5]=[O:22]
Reactant: O
Reactant: BrCc1cc(Br)cc(Br)c1
Agent: C1N2CN3CN1CN(C2)C3
Agent: Cl
Solvent: CC(=O)O
Product: O=Cc1cc(Br)cc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To 3,5-dibromobenzylbromide (Lancaster) (20 g, 0.061 mole) in H2O (27 mL) and glacial acetic acid (27 mL) was added hexamethylenetetramine (Aldrich). The reaction mixture was heated at reflux for 2 hours. Concentrated HCl (22 mL) was then added and the refluxing was continued for 30 minutes. After cooling to room temperature, the reaction mixture was poured into H2O (230 mL) and stirred for 10 minutes. The resulting precipitate was filtered, washed with H2O and dried to yield 3,5-dibromobenzaldehyde (11.45 g) as a white solid. MS and NMR were consistent with the desired structure.
Reaction SMILES: [Br:1][C:2]1[C:3]([S:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[CH:5]=O.Cl.[NH2:17][OH:18]>C(O)(C)C.O>[Br:1][C:2]1[C:3]([S:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[CH:5]=[N:17][OH:18]
Reactant: NO
Reactant: CC(C)(C)Sc1c(Br)cc(F)cc1C=O
Agent: Cl
Solvent: CC(C)O
Solvent: O
Product: CC(C)(C)Sc1c(Br)cc(F)cc1C=NO
Temperature: 90 °C

Procedure:
A mixture of 3-bromo-2-tert-butylsulfanyl-5-fluorobenzaldehyde (4 g, 13.7 mmol) and hydroxylamine hydrochloride in isopropanol (160 mL) and water (33 mL) was heated to 90° C. for 16 h. The reaction mixture was cooled and 2-propanol was removed in vacuo. Water was added to residue, followed by saturated aqueous sodium bicarbonate until the pH was ˜8. The mixture was extracted with dichloromethane (2×30 mL). The combined organic fractions were dried sodium sulfate, filtered, and concentrated to afford 3.8 g of the crude title compound, which was used without further purification.
Reaction SMILES: Cl.[OH:2][C:3]1[CH:15]=[CH:14][C:6]2[S:7][C:8]([C:11]([OH:13])=[O:12])=[C:9]([CH3:10])[C:5]=2[CH:4]=1.[CH3:16]O>>[OH:2][C:3]1[CH:15]=[CH:14][C:6]2[S:7][C:8]([C:11]([O:13][CH3:16])=[O:12])=[C:9]([CH3:10])[C:5]=2[CH:4]=1
Reactant: Cc1c(C(=O)O)sc2ccc(O)cc12
Reactant: CO
Agent: Cl
Product: COC(=O)c1sc2ccc(O)cc2c1C

Procedure:
Dry HCl gas is bubbled through a solution of 5-hydroxy-3-methylbenzo(b)thiophene-2-carboxylic acid (1.0 g, 4.81 mmol) in methanol (150 ml) for 1 hour at room temperature. The brown solution is refluxed for 2 hours and concentrated. Extraction with ether, washing with water, aqueous sodium bicarbonate, water and bring, drying (MgSO4) and concentration affords the crude product which is subjected to flash chromatography over silica gel. Elution with 33% ethyl acetate in hexane affords methyl 5-hydroxy-3-methylbenzo(b)thiophene-2-carboxylate.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([N+:11]([O-:13])=[O:12])=[CH:4][N:3]=1.[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>C1COCC1>[N:14]1([C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([N+:11]([O-:13])=[O:12])=[CH:4][N:3]=2)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1
Reactant: C1COCCN1
Reactant: O=[N+]([O-])c1cnc(Cl)c([N+](=O)[O-])c1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cnc(N2CCOCC2)c([N+](=O)[O-])c1
Temperature: 60 °C
Yield: 97.8 %

Procedure:
5 g (24.5 mmol) of 2-chloro-3,5-dinitropyridine, 40 ml of THF and 50 mmol of morpholine were placed in a round-bottomed flask. The mixture was maintained at 60° C. for 15 hours with stirring and was then poured into an ice-water mixture with stirring. The precipitate formed was filtered off by suction and dried under vacuum to constant weight. 6.09 g of yellow powder were obtained.
Reaction SMILES: CC1[N:3]([C:8]2[N:13]=[CH:12][C:11]([CH:14]([OH:17])[CH2:15][CH3:16])=[CH:10][CH:9]=2)C(C)=CC=1.Cl.NO.[CH2:21](O)[CH3:22]>O>[NH2:3][C:8]1[CH:9]=[CH:10][C:11]([CH:14]([O:17][CH2:21][CH3:22])[CH2:15][CH3:16])=[CH:12][N:13]=1
Reactant: CCO
Reactant: CCC(O)c1ccc(-n2c(C)ccc2C)nc1
Agent: Cl
Agent: NO
Solvent: O
Product: CCOC(CC)c1ccc(N)nc1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
To a solution of 1.07 g of 1-[6-(2,5-dimethylpyrrol-1-yl)pyridin-3-yl]propan-1-ol in 20 mL of ethanol heated to 80° C. is added a solution of 1.94 g of hydroxylamine hydrochloride in 1.6 mL of water, and the mixture is stirred for 24 hours at 80° C. After cooling to room temperature, the reaction medium is filtered and concentrated to dryness. The residue is purified by flash chromatography on a column of 100 g of silica, eluting with 400 mL of dichloromethane, then with 300 mL of ethyl acetate and then with a 95/5 mixture of dichloromethane and methanol. The fractions containing the expected product are combined and concentrated under vacuum to give 0.186 g of 2-amino-5-(1-ethoxypropyl)pyridine in the form of a brown oil.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]2[C:11]=1[I:12].[OH:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[I:12][C:11]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[CH2:2][O:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17]
Reactant: COC(=O)c1ccccc1O
Reactant: ClCc1nc2ccccn2c1I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccccc1OCc1nc2ccccn2c1I
Yield: 45.7 %

Procedure:
4 g (13.68 mmol) of 2-(chloromethyl)-3-iodoimidazo[1,2-a]pyridine were dissolved in dimethylformamide with magnetic stirring and then 2.71 ml (20.51 mmol) of methyl 2-hydroxybenzoate and 6.68 g (20.51 mmol) of cesium carbonate were added. The mixture was stirred at 60° C. for 2 h before being poured into 200 ml of water. The aqueous phase was extracted with 2×100 ml of ethyl acetate. The combined organic phases were washed with 100 ml of a saturated NaHCO3 aqueous solution, 100 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was triturated in 50 ml of diisopropyl ether, the obtained solid was isolated by filtration. 2.55 g of expected product were isolated. On the other hand, an aqueous phase suspension was isolated by filtration and washed with 2×30 ml of water. The analyses confirmed that this was also the expected product. Both batches were therefore collected and 5.58 g (yield=76%) of methyl 2-((3-iodoimidazo[1,2-a]pyridin-2-yl) methoxy)benzoate were obtained as a white powder. LC-MS: m/z=409 (MH+); UV purity at 254 nm=98%. 1H NMR (300 MHz, DMSO) δ 8.33 (d, J=6.9 Hz, 1H), 7.69-7.44 (m, 3H), 7.45-7.28 (m, 2H), 7.16-6.93 (m, 2H), 5.23 (s, 2H), 3.73 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.I[C:15]1[C:23]2[C:18](=[N:19][CH:20]=[N:21][C:22]=2[NH2:24])[N:17]([CH:25]([CH3:27])[CH3:26])[N:16]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:25]([N:17]1[C:18]2=[N:19][CH:20]=[N:21][C:22]([NH2:24])=[C:23]2[C:15]([C:4]2[CH:5]=[CH:6][CH:7]=[C:8]([O:9][CH3:10])[C:3]=2[O:2][CH3:1])=[N:16]1)([CH3:27])[CH3:26]
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Reactant: COc1cccc(B(O)O)c1OC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Product: COc1cccc(-c2nn(C(C)C)c3ncnc(N)c23)c1OC
Temperature: 80 °C
Yield: 87.4 %

Procedure:
A solution 2,3-dimethoxyphenylboronic acid (105 mg, 0.58 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (70 mg, 0.23 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA65 (63 mg, 88% yield). ESI-MS (M+H)+ m/z calcd 314.1, found 314.1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([C:34]1([C:39]#[N:40])[CH2:38][CH2:37][CH2:36][CH2:35]1)(=[O:33])=[O:32]>>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[S:31]([C:34]3([C:39]#[N:40])[CH2:38][CH2:37][CH2:36][CH2:35]3)(=[O:33])=[O:32])=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C
Reactant: N#CC1(S(=O)(=O)c2ccccc2Br)CCCC1
Product: N#CC1(S(=O)(=O)c2ccccc2-c2ccc(-c3cnc(N)cn3)c(F)c2)CCCC1

Procedure:
The title compound was prepared using conditions analogous to those used to make Example 6 utilizing 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 1-((2-bromophenyl)sulfonyl)cyclopentanecarbonitrile. MS (ESI): mass calcd. for C22H19FN4O2S, 422.12; m/z found, 423.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.40 (s, 1H), 8.21 (dd, J=8.0, 1.0, 1H), 8.03 (d, J=1.4, 1H), 7.92 (m, 1H), 7.88-7.80 (m, 2H), 7.53 (d, J=7.6, 1H), 7.35 (dd, J=12.3, 1.5, 1H), 7.29 (dd, J=8.0, 1.6, 1H), 6.74 (s, 2H), 2.21-2.04 (m, 4H), 1.71-1.67 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([C:11]3[CH:16]=[CH:15][C:14]([C@H:17]4[CH2:20][C@H:19](O)[CH2:18]4)=[CH:13][CH:12]=3)[C:7]([CH2:9][CH3:10])=[N:8][C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P([N:58]=[N+:59]=[N-:60])(C2C=CC=CC=2)=O)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([C:11]3[CH:16]=[CH:15][C:14]([C@@H:17]4[CH2:20][C@H:19]([N:58]=[N+:59]=[N-:60])[CH2:18]4)=[CH:13][CH:12]=3)[C:7]([CH2:9][CH3:10])=[N:8][C:4]=2[CH:3]=1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CCc1nc2cc(Cl)c(Cl)cc2n1-c1ccc([C@H]2C[C@H](O)C2)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCc1nc2cc(Cl)c(Cl)cc2n1-c1ccc([C@H]2C[C@@H](N=[N+]=[N-])C2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 81.9 %

Procedure:
To a stirred solution of trans-3-[4-(5,6-dichloro-2-ethyl-1H-benzimidazol-1-yl)phenyl]cyclobutanol (step 8, 572 mg, 1.6 mmol), triphenylphosphine (623 mg, 2.4 mmol) and diphenylphosphoryl azide (DPPA) (655 mg, 2.4 mmol) in THF (8 mL) was added diethyl azodicarboxylate (415 mg, 2.4 mmol) at room temperature. The resulting mixture was stirred at room temperature for 3 h, then the mixture was diluted with ethyl acetate (100 mL) and washed with water (100 mL) and brine (100 mL). The organic layer was dried (Na2SO4), and concentrated. Purification by flash column chromatography on silica gel eluting with hexane/ethyl acetate (2:1) to afford 506 mg (83%) of the title compound as colorless solids: MS (EI) m/z: 385 (M+); 1H-NMR (CDCl3) δ 7.84 (1H, br.s), 7.42 (2H, d, J=8.3 Hz), 7.28 (2H, d, J=8.3 Hz), 7.17 (1H, br.s), 3.98–3.88 (1H, m), 3.37–3.25 (1H, m), 2.89–2.75 (2H, m), 2.77 (2H, q, J=7.6 Hz), 2.34–2.23 (2H, m), 1.34 (3H, t, J=7.6 Hz).