Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:4](=[O:38])[C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][N:17](S(C4C=CC(C)=CC=4)(=O)=O)[C:14]3=[N:15][CH:16]=2)[CH:8]=[N:7][CH:6]=1)C.[CH:39]([NH2:42])([CH3:41])[CH3:40]>>[CH:39]([NH:42][C:4](=[O:38])[C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[CH:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:8]=[N:7][CH:6]=1)([CH3:41])[CH3:40]
Reactant: CC(C)N
Reactant: CCOC(=O)c1cncc(-c2cnc3c(c2)c(-c2ccccc2OC)cn3S(=O)(=O)c2ccc(C)cc2)c1
Product: COc1ccccc1-c1c[nH]c2ncc(-c3cncc(C(=O)NC(C)C)c3)cc12
Reaction time: 48 h
Yield: 35 %

Procedure:
Into a 5 mL screw-cap vial were added 5-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester (50.2 mg, 0.095 mmol) and isopropylamine (500 μL). The vial was sealed and placed in heated block at 100° C. for 48 h. The reaction solution was concentrated and the residue was dissolved in 1:1 MeOH/acetone (2 mL total) and treated with 100 μL of 50% w/w KOH(aq) for 1 h. Glacial Acetic acid was added to obtain pH 7, then the reaction mixture was concentrated. The residue was partitioned between EtOAc and water, then the layers were separated, and the organic phase was washed 2× with water. The organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate (containing 10% MeOH) and hexanes afforded the title compound as a white powder (13 mg, 35%). 1H-NMR (500 MHz, d6-DMSO) δ=11.96 (br. s, 1H), 9.05 (d, J=2.5 Hz, 1H), 8.94 (d, J=2.0 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H), 8.51 (d, J=8.0 Hz, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.30 (d, J=2.0 Hz, 1H), 7.76 (s, 1H), 7.61 (d, J=5.5 Hz, 1H), 7.29 (dd, J=2, 7.5 Hz, 1H), 7.12 (d, J=7.5 1H), 7.04 (d, J=7.5 Hz, 1H), 4.11 (m, 1H), 3.84 (s, 3H), 1.17 (s, 6H); MS: m/z 387.1 [M+].
Reaction SMILES: [C:1](=[O:29])([O:3][CH2:4][C:5]1[N:6]([CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[C:7]([S:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[CH:15]=2)=[C:8]([CH:10]([CH3:12])[CH3:11])[N:9]=1)[NH2:2].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.[CH2:36]=O>C(OCC)(=O)C>[O:33]1[CH2:34][CH2:35][N:30]([CH2:36][NH:2][C:1](=[O:29])[O:3][CH2:4][C:5]2[N:6]([CH2:22][C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[C:7]([S:13][C:14]3[CH:15]=[C:16]([Cl:21])[CH:17]=[C:18]([Cl:20])[CH:19]=3)=[C:8]([CH:10]([CH3:12])[CH3:11])[N:9]=2)[CH2:31][CH2:32]1
Reactant: C1COCCN1
Reactant: CC(C)c1nc(COC(N)=O)n(Cc2ccncc2)c1Sc1cc(Cl)cc(Cl)c1
Reactant: C=O
Solvent: CCOC(C)=O
Product: CC(C)c1nc(COC(=O)NCN2CCOCC2)n(Cc2ccncc2)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Yield: 68.8 %

Procedure:
A suspension of the compound 111 (306 mg, 0.7 mmol), morpholine (61.0 mg, 0.7 mmol) and paraformaldehyde (22.0 mg, 0.733 mmol) in ethyl acetate (4 mL) was heated under reflux in an atmosphere of nitrogen for 3 days. After cooling down at room temperature, the residue was purified by chromatography on a silica gel column (eluate: ethyl acetate - methanol (5:1)) to give the compound 113 (265 mg, 69%). Rf 0.63 (5:1 EtOAc-CH3OH). 1H-NMR (CDCl3): δH1.30 (6 H, d, J 6.9 Hz, (CH3)2CH), 2.44 (4H, m, N(CH2CH2)2O), 3.18 (1 H, sep, J 6.9 Hz, (CH3)2CH), 3.65 (4 H, m, N(CH2CH2)2O), 3.91 (2 H, d, J 6.6 Hz, NCH2NH), 4.98 (1 H, t, J 6.6 Hz, NCH2NH ), 5.19 (2 H, s, CH2O), 5.25 (2 H, s, NCH2 ), 6.69 (2 H, d, J 1.8 Hz, arom 2- and 6-H), 6.71 (2 H, d-like, 4-pyridyl 2- and 6-H), 7.05 (1 H, t, J 1.8 Hz, arom 4-H), 8.45 (2 H, d-like, 4-pyridyl 3- and 5-H). Elementary analysis (for C25H29N5O2SCl2) Calcd. : C, 54.55% H, 5.31% N, 12.72% S, 5.82% Cl, 12.88% Found: C, 54.37% H, 5.36% N, 12.80% S, 5.92% Cl, 12.64% hydrochloride of 113 Elementary analysis (for C25H32N5O3SCl5 3HCl 3H2O) Calcd. : C, 42.06% H, 5.36% N, 9.81% S, 4.40% Cl, 24.83% Found: C, 42.01% H, 5.34% N, 10.01% S, 4.73% Cl, 24.92%.
Reaction SMILES: Br[C:2]1[S:10][C:9]2[C:8]([Cl:11])=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14]>C1COCC1.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I>[Cl:11][C:8]1[C:9]2[S:10][C:2]([C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12])=[CH:3][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: C#C[Si](C)(C)C
Reactant: Clc1ncnc2cc(Br)sc12
Agent: Cl[Pd]Cl
Agent: [Cu]I
Solvent: N#Cc1ccccc1
Solvent: C1CCOC1
Product: C[Si](C)(C)C#Cc1cc2ncnc(Cl)c2s1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
A mixture of 6-bromo-4-chloro-thieno[3,2-d]pyrimidine (10.0 mmol), (trimethylsilyl)acetylene (12.0 mmol), Pd(PhCN)2Cl2, (1.0 mmol), CuI (1.0 mmol) and TEA (2.0 mmol) in dry THF (60.0 mL) was flushed with dry N2 for several minutes and stirred at 60° C. for 30 minutes under an atmosphere of N2. The solvent was removed and the residue purified by flash column chromatography on silica gel to provide 4-chloro-6-trimethylsilanylethynyl-thieno[3,2-d]pyrimidine (compound 48.1) in 65% yield. EIMS (m/z): calcd. for C11H11ClN2SSi (M+)+H 266.01. found 266.00.
Reaction SMILES: [N+:1]([C:4]1[C:5](O)=[C:6]2[S:12][CH:11]=[CH:10][C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2].P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:5]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=[C:7]2[CH:10]=[CH:11][S:12][C:6]=12
Reactant: O=[N+]([O-])c1cnc2ccsc2c1O
Reactant: O=P(Cl)(Cl)Cl
Product: O=[N+]([O-])c1cnc2ccsc2c1Cl
Yield: 74 %

Procedure:
6-Nitrothieno[3,2-b]pyridin-7-ol (3.3 g, 17 mmol) was suspended in phosphoryl chloride (30 mL, 400 mmol) and heated at reflux for 1 h (dissolution was apparent after 45 min) The solvent was removed. Toluene was added to the residue and the volatiles were removed in vacuo. Dichloromethane and sat. NaHCO3 solution were added (Caution: gas evolution), and the layers separated. The organic layer was washed with water, dried over MgSO4 and concentrated to give the desired product (2.7 g, 75%). LCMS calculated for C7H4ClN2O2S (M+H)+: m/z=215.0. Found: 214.9.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].[NH2:18][C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[N:24][NH:25]2)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCO>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][C:3]([C:16]#[N:17])=[C:2]2[NH:18][C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[N:24][NH:25]2)=[CH:21][CH:20]=1
Reactant: Nc1ccc2cn[nH]c2c1
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1OC
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCO
Product: COc1cc2ncc(C#N)c(Nc3ccc4cn[nH]c4c3)c2cc1OC
Temperature: 100 °C
Yield: 106.3 %

Procedure:
A solution of 500 mg (2.00 mM) of 4-chloro-6,7-dimethoxy-quinoline-3-carbonitrile and 975 mg (2.61 mM) of 6-aminoindazole in 15 ml of 2-methoxyethanol was refluxed for 3 hours. To the warm solution was added 1 ml of 1M sodium carbonate and the sample was heated for 5 minutes at 100° C., then poured into 300 ml of ice water. The solid was collected, washed with water followed by ether and dried under vacuum at 80° C. to yield 738 mg of the title compound as a tan solid: mass spectrum (electrospray, m/e): M+H 345.9, mp=180-183° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH:9]([NH:16][CH3:17])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:3]=1.ClC(Cl)(O[C:22](=[O:28])OC(Cl)(Cl)Cl)Cl.O.CCOC(C)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[NH:8][C:22](=[O:28])[N:16]([CH3:17])[CH:9]2[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CNC(c1ccccc1)c1cc(Br)ccc1N
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CN1C(=O)Nc2ccc(Br)cc2C1c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of reactant 4-Bromo-2-(methylamino-phenyl-methyl)-phenylamine (3.4 g, 12 mmol) in THF (150 mL) is added triphosgene (3.81 g, 13 mmol). After the addition the mixture is stirred at r.t. for 3 h. Then H2O is added and is extacd with EtOAc, dried over Na2SO4 and concentrated. The residue is purified by chromatography on silica gel to give product.