Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]4[OH:32])=[CH:21][C:20]=3[OH:33])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:34](Cl)(=[O:46])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45].N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:13]1([C:11]2[N:12]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]4[O:32][C:34](=[O:46])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])=[CH:21][C:20]=3[OH:33])[N:10]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: Oc1cc(OC2CCCCC2O)ccc1-c1nc(-c2ccccc2)nc(-c2ccccc2)n1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCCCCCCCCCCC(=O)OC1CCCCC1Oc1ccc(-c2nc(-c3ccccc3)nc(-c3ccccc3)n2)c(O)c1
Reaction time: 20 h

Procedure:
A mixture of 5.0 g (11.3 mmol) of 2,4-diphenyl-6-(2'-hydroxy-4'-(2"- hydroxycyclohexyloxy)phenyl)-1,3,5-triazine, 5.7 g (26 mmol) of dodecanoyl chloride (Fluka, 98%) and 0.1 g (1.3 mmol) of pyridine in 60 ml of toluene is stirred under nitrogen and kept at 50° C. for 20 h.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9](Br)=[CH:8]2)(=O)C.[NH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:16]1([C:9]2[CH:10]=[N:11][C:12]3[C:7]([CH:8]=2)=[CH:6][C:5]([OH:4])=[CH:14][CH:13]=3)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1
Reactant: CC(=O)Oc1ccc2ncc(Br)cc2c1
Reactant: C1COCCN1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: Cc1ccccc1
Product: Oc1ccc2ncc(N3CCOCC3)cc2c1
Temperature: 100 °C
Yield: 44.7 %

Procedure:
A mixture of Intermediate A (0.8 g, 3.01 mmol), morpholine (1.048 g, 12.03 mmol), Pd2(dba)3 (0.275 g, 0.301 mmol), xantphos (0.305 g, 0.602 mmol) and KOtBu (0.337 g, 3.01 mmol) in toluene (15 ml) was bubbled with N2 for 15 min and then was heated at 100° C. for 5 h under MW radiation. The mixture was quenched with saturated aqueous NaHCO3 solution. The aqueous phase was extracted with DCM/IPA (10 ml, v/v=3/1) for 3 times. The combined extract was dried over anhydrous MgSO4. Filtered and concentrated, the residue was purified by silica gel chromatography to afford the title compound (0.31 g, 40.3% yield). LCMS (method B): [M+H]+=231, tR=1.1 min.
Reaction SMILES: [C:1]([C:3]1[CH:22]=[CH:21][C:6]2[CH:7]=[CH:8][N:9]3[CH:20]=[CH:19][CH:18]=[C:10]3[C:11](=[CH:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])[C:5]=2[CH:4]=1)#N.C[OH:24]>>[CH:1]([C:3]1[CH:22]=[CH:21][C:6]2[CH:7]=[CH:8][N:9]3[CH:20]=[CH:19][CH:18]=[C:10]3[C:11](=[CH:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])[C:5]=2[CH:4]=1)=[O:24]
Reactant: CN(C)CCC=C1c2cc(C#N)ccc2C=Cn2cccc21
Reactant: CO
Product: CN(C)CCC=C1c2cc(C=O)ccc2C=Cn2cccc21

Procedure:
Similarly, by substituting 9-cyano-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or its intermediate carbinol as starting material, there is produced 9-formyl-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][C@@H:9]([OH:12])[C@H:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7]1)=[O:5])[CH3:2].[F:19][C:20]1[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1C=CC=CC=1>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][C@H:9]([O:12][C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)[C@H:8]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:7]1)=[O:5])[CH3:2]
Reactant: Oc1ccc(F)cc1
Reactant: CCOC(=O)N1CC[C@@H](O)[C@H](c2ccccc2)C1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: CCOC(=O)N1CC[C@H](Oc2ccc(F)cc2)[C@H](c2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred mixture of 8.73 g of trans-1-ethoxycarbonyl-3-phenyl-4-piperidinol, 4.32 g of 4-fluorophenol, 10.1 g of triphenylphosphine and 350 ml of benzene is added dropwise, at 5° C. under nitrogen, a solution of 6.71 g of diethyl azodicarboxylate in 350 ml of benzene. After the addition is complete, the mixture is stirred overnight at room temperature. The reaction mixture is processed according to the procedure of Example 70 to give product as a gum.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11])(=[O:4])=[O:3].[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[O:18]1[CH2:19][CH2:20][N:15]([S:2]([C:5]2[CH:6]=[N:7][CH:8]=[C:9]([CH:14]=2)[C:10]([O:12][CH3:13])=[O:11])(=[O:4])=[O:3])[CH2:16][CH2:17]1
Reactant: C1COCCN1
Reactant: COC(=O)c1cncc(S(=O)(=O)Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)c1cncc(S(=O)(=O)N2CCOCC2)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 60.4 %

Procedure:
Methyl 5-(chlorosulfonyl)nicotinate (35 mg, 0.149 mmol) was added to the morpholine (25.9 mg, 0.297 mmol) in presence of Potassiumcarbonate (41.1 mg, 0.297 mmol) in THF (8 mL) at room temperature and the reaction mixture was stirred for 12 h at room temperature. The reaction was monitored by TLC, after completion of the reaction, Solvent was removed by vacuum and then compound was purified by column chromatography (2% Methanol/DCM) afforded the product methyl 5-(morpholinosulfonyl)nicotinate (26 mg, 0.090 mmol, 60.5% yield) as a solid. 1HNMR (400 MHz, CDCl3): δ 9.41 (s, 1H), 9.12 (s, 1H), 8.60 (d, 1H, J=2.0 Hz), 4.01 (s, 3H), 3.76 (m, 4H), 3.07 (m, 4H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:21])[C:9]2[CH:20]=[CH:19][C:12]3[N:13]([CH3:18])[C:14]([NH:16][CH3:17])=[N:15][C:11]=3[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([S:29]([NH2:32])(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=1>>[CH3:21][N:8]([C:9]1[CH:20]=[CH:19][C:12]2[N:13]([CH3:18])[C:14]([NH:16][CH3:17])=[N:15][C:11]=2[CH:10]=1)[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:22][C:23]2[CH:24]=[C:25]([S:29]([NH2:32])(=[O:30])=[O:31])[CH:26]=[CH:27][CH:28]=2)[N:7]=1
Reactant: CNc1nc2cc(N(C)c3ccnc(Cl)n3)ccc2n1C
Reactant: Nc1cccc(S(N)(=O)=O)c1
Product: CNc1nc2cc(N(C)c3ccnc(Nc4cccc(S(N)(=O)=O)c4)n3)ccc2n1C

Procedure:
The title compound was prepared following the procedure of Example 1 with N5-(2-chloropyrimidin-4-yl)-N2,N5,1-trimethyl-1H-benzimidazole-2,5-diamine (60 mg, 0.20 mmol) and 3-amino-benzenesulfonamide (34 mg, 0.20 mmol) as a white solid (40 mg, 42%). 1H NMR (300 MHz, d6-DMSO+NaHCO3) δ 9.51 (s, 1H), 8.61 (s, 1H), 7.77-7.82 (M, 2H), 7.26-7.39 (m, 6H), 7.17 (s, 1H), 6.92 (d, J=7.8 Hz, 1H), 5.66 (d, J=6.0 Hz, 1H), 3.55 (s, 3H), 3.47 (s, 3H), 2.95 (d, J=4.2 Hz, 3H). MS (ESI) m/z=439 [M+H]+.
Reaction SMILES: [OH-].[Na+].[CH3:3][N:4]1[CH:8]=[C:7]([C:9]2[CH:32]=[CH:31][C:12]3[N:13]([C:16]4[CH:17]=[C:18]([NH:27]C(=O)C)[CH:19]=[C:20]([N:22]5[CH:26]=[CH:25][CH:24]=[CH:23]5)[CH:21]=4)[CH:14]=[N:15][C:11]=3[CH:10]=2)[N:6]=[N:5]1>C(O)C.C(OCC)(=O)C>[CH3:3][N:4]1[CH:8]=[C:7]([C:9]2[CH:32]=[CH:31][C:12]3[N:13]([C:16]4[CH:17]=[C:18]([CH:19]=[C:20]([N:22]5[CH:26]=[CH:25][CH:24]=[CH:23]5)[CH:21]=4)[NH2:27])[CH:14]=[N:15][C:11]=3[CH:10]=2)[N:6]=[N:5]1
Reactant: CC(=O)Nc1cc(-n2cccc2)cc(-n2cnc3cc(-c4cn(C)nn4)ccc32)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cn1cc(-c2ccc3c(c2)ncn3-c2cc(N)cc(-n3cccc3)c2)nn1
Yield: 73 %

Procedure:
A mixture of 20% sodium hydroxide (5 ml) and the compound of Example 99 (1.0 g, 2.52 mmol) in 10 ml ethanol was heated at 100° C. for 3 h. The mixture was diluted with ethyl acetate (100 ml) and the organic layer was washed with water (50 ml) and brine (25 ml). The solvent was removed under reduced pressure and the residue was purified by column chromatography over silica gel to afford the product in 73% yield (0.65 g). LC-MS (ESI): Calculated mass: 355.4; Observed mass: 356.3 [M+H]+ (rt: 0.49 min).
Reaction SMILES: [F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1.[CH2:20]([CH:22]([CH2:26][CH3:27])[CH2:23][CH2:24][NH2:25])[CH3:21].[BH4-].[Na+]>CO>[CH2:20]([CH:22]([CH2:26][CH3:27])[CH2:23][CH2:24][NH:25][CH2:18][C:16]1[CH:15]=[CH:14][C:3]([O:4][C:5]2[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=2)=[C:2]([F:1])[CH:17]=1)[CH3:21]
Reactant: NC(=O)c1cnc(Oc2ccc(C=O)cc2F)cn1
Reactant: CCC(CC)CCN
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCC(CC)CCNCc1ccc(Oc2cnc(C(N)=O)cn2)c(F)c1
Reaction time: 8 h
Yield: 62 %

Procedure:
Place 5-(2-fluoro-4-formylphenoxy)pyrazine-2-carboxamide (Example 737, Part E) (0.400 g, 1.53 mmol), 3-ethylpentylamine (0.194 g, 1.68 mmol) (Example 733, Part B) and 3 Å molecular sieves in a vial. Add methanol (7.7 mL), cap and stir overnight. Add NaBH4 (0.058 g, 1.53 mmol) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 15% (2.0 M NH3 in methanol) in 80% (ethyl acetate in hexanes) to give the title compound (0.342 g, 62%): TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C19H26N4O2F 361.2040 (M+H)+, found 361.2048, time 0.57 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min. 20-95% over 18], tR=12.0 min, 96.9% purity.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[CH:6][C:7]2[NH:8][C:9]3[C:14]([C:15]=2[CH:16]=1)=[CH:13][C:12]([Br:17])=[CH:11][CH:10]=3.[Br:18][CH2:19][CH2:20][CH2:21][CH2:22]Br>CN(C=O)C>[Br:17][C:12]1[CH:11]=[CH:10][C:9]2[N:8]([CH:19]([Br:18])[CH2:20][CH2:21][CH3:22])[C:7]3[C:15]([C:14]=2[CH:13]=1)=[CH:16][C:4]([Br:3])=[CH:5][CH:6]=3
Reactant: BrCCCCBr
Reactant: Brc1ccc2[nH]c3ccc(Br)cc3c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCC(Br)n1c2ccc(Br)cc2c2cc(Br)ccc21
Reaction time: 0.08 h
Yield: 65 %

Procedure:
Under a nitrogen atmosphere, sodium hydride (0.3 g, 12.5 mmol, Aldrich) was added to a solution of 3,6-dibromo-9H-carbazole (2 g, 6.1 mmol, Aldrich) in DMF (10 ml). The mixture was stirred for 5 min, 1,4-dibromobutane (3.9 g, 18 mmol, Aldrich) was added, and the mixture was refluxed for 12 h. Flash chromatography (N-hexane/ethyl acetate 2:1) gave 3,6-dibromo-9-(1-bromobutyl)carbazole (yield: 65%). A solution of the obtained compound (1.84 g, 4 mmol) and piperidine (0.68 g, 8 mmol, Aldrich) in ethanol (30 ml) was refluxed in the presence of a trace of NaI for 24 h. The product of the reaction was purified by column chromatography (n-Hexane/ethyl acetate 1:2) and added into a high pressure flask containing a mixture of palladium(II) acetate (0.005 g, 0.02 mmol, Aldrich) and tri-o-tolylphosphine (0.04 g, 0.13 mmol, Aldrich). After addition of triethylamine (5 ml), acetonitrile (10 ml), and 4-vinylpyridine (0.53 g, 5 mmol, Aldrich), the flask was sealed, nitrogen was bubbled for 5 min, and the reaction was kept at ˜105° C. for 48 h. The precipitate was collected, extracted twice with H2O and CH2Cl2, dried over anhydrous MgSO4, dissolved in THF, filtered, and the product was recrystallized from acetone. A solution of this product (0.5 g, 1 mmol) in DMF (10 ml) was refluxed with an excess of CH3I for 6 h, and the resulting product was recrystallized twice from methanol (35% overall yield, 300° C.). 1H NMR (400 MHz, DMSO-d6) δ: 8.83 (d, J=6 Hz, 4H), 8.62 (s, 2H), 8.23 (d, J=12.4 Hz, 2H), 8.20 (d, J=4.4 Hz, 4H), 7.96 (d, J=8.4 Hz, 2H), 7.82 (d, J=8.4 Hz, 2H), 7.57 (d, J=15.6 Hz, 2H), 4.52 (t, 2H), 4.25 (s, 6H), 2.94 (s, 3H), 2.25 (t, 4H), 2.21 (t, 2H), 1.84 (m, 4H), 1.53 (m, 4H), 1.48 (m, 2H). EA (C38H45I3N4.0.5H2O): calc (obs %) C, 48.17 (48.03); H, 4.89 (4.91); N, 5.91 (5.86).