Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:12]3[C:7](=[N:8][CH:9]=[CH:10][CH:11]=3)[N:6]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)[C:5]=12.[H-].[Na+].[CH3:22][N:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[N:25]=[C:24]1S(C)(=O)=O.O>CN(C=O)C>[CH3:22][N:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[N:25]=[C:24]1[O:19][C:16]1[CH:17]=[CH:18][C:13]([N:6]2[C:7]3=[N:8][CH:9]=[CH:10][CH:11]=[C:12]3[N:4]3[CH:3]=[CH:2][N:1]=[C:5]23)=[CH:14][CH:15]=1
Reactant: Cn1c(S(C)(=O)=O)nc2cccnc21
Reactant: Oc1ccc(-n2c3ncccc3n3ccnc23)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1c(Oc2ccc(-n3c4ncccc4n4ccnc34)cc2)nc2cccnc21
Reaction time: 0.17 h
Yield: 67.1 %

Procedure:
To a solution of 4-(9H-imidazo[1′,2′:1,2]imidazo[4,5-b]pyridin-9-yl)phenol (175 mg) obtained in Example 9, step C) in DMF (2 ml) was added sodium hydride (60% in oil, 32 mg) at room temperature by small portions. After stirring for 10 min, a solution of 3-methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (169 mg) in DMF (1.5 ml) was added, and the obtained mixture was stirred under microwave irradiation at 180° C. for 30 min. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (THF) and recrystallized from methanol/water to give the title compound (179 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].[NH2:13][C:14]1[C:15]2[C:22]([C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([NH2:31])[CH:26]=3)=[O:24])=[CH:21][N:20]([CH:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[C:16]=2[N:17]=[CH:18][N:19]=1>N1C=CC=CC=1>[NH2:13][C:14]1[C:15]2[C:22]([C:23]([C:25]3[CH:26]=[C:27]([NH:31][S:9]([C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[Cl:1])(=[O:11])=[O:10])[CH:28]=[CH:29][CH:30]=3)=[O:24])=[CH:21][N:20]([CH:32]3[CH2:33][CH2:34][CH2:35][CH2:36]3)[C:16]=2[N:17]=[CH:18][N:19]=1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1Cl
Reactant: Nc1cccc(C(=O)c2cn(C3CCCC3)c3ncnc(N)c23)c1
Solvent: c1ccncc1
Product: Nc1ncnc2c1c(C(=O)c1cccc(NS(=O)(=O)c3ccc(F)cc3Cl)c1)cn2C1CCCC1
Temperature: 120 °C
Yield: 24.9 %

Procedure:
2-Chloro-4-fluorobenzenesulphonyl chloride (85.7 mg, 0.37 mmol) was added to a solution of (4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(3-amino-phenyl)-methanone (80 mg, 0.25 mmol) in pyridine (3 mL). The resulting solution was heated to 120° C. for 3 h. The reaction was quenched with water and concentrated. The residue was dissolved in EtOAc and washed with 1N NaOH (1×) and water (1×). The organic layer was dried over Na2SO4 and concentrated. Purification by flash column chromatography (CH2Cl2/MeOH 98:2) afforded the title compound as a white solid (32 mg, 25%). MS: 514.1/516.1 (MH+); HPLC Rf: 6.12 min. (HPLC method 4).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[N:3]=1.[CH3:17][N:18]([CH3:28])[CH2:19][CH2:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1>>[ClH:1].[Cl:16][C:12]1[CH:11]=[C:10]([C:4]2[N:3]=[C:2]([NH:25][C:24]3[CH:23]=[CH:22][C:21]([CH2:20][CH2:19][N:18]([CH3:17])[CH3:28])=[CH:27][CH:26]=3)[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]=2)[CH:15]=[CH:14][CH:13]=1
Reactant: CN(C)CCc1ccc(N)cc1
Reactant: CCc1cc(Cl)nc(-c2cccc(Cl)c2)n1
Product: CCc1cc(Nc2ccc(CCN(C)C)cc2)nc(-c2cccc(Cl)c2)n1
Product: Cl
Yield: 73.3 %

Procedure:
Following general procedure B1, 4-chloro-2-(3-chlorophenyl)-6-ethylpyrimidine (0.085 g, 0.33 mmol) was reacted with 4-(2-(dimethylamino)ethyl)aniline (0.066 g, 0.40 mmol), followed by formation of the hydrochloride salt to afford the title compound (0.101 g, 72%) as a light yellow solid. MW=417.37. 1H NMR (DMSO-d6, 500 MHz) δ 9.60 (s, 1H), 8.35-8.27 (m, 2H), 7.66 (d, J=8.5 Hz, 2H), 7.59-7.52 (m, 2H), 7.26 (d, J=8.5 Hz, 2H), 6.60 (s, 1H), 2.91-2.78 (m, 4H), 2.67 (q, J=7.5 Hz, 2H), 1.26 (t, J=7.5 Hz, 3H); APCI MS m/z 381 [M+H]+.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2.C1(C)C=C(C)C=C(C)C=1S(O[NH2:25])(=O)=O.O>O1CCCC1>[Cl:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[NH2:25]
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Reactant: Clc1cccc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Nn1ccc2c(Cl)cccc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 94.3 %

Procedure:
Sodium hydride (60 %wt suspension in mineral oil; 0.86 g, 21.5 mmol) is suspended in dry tetrahydrofuran (THF, 20 mL) and is cooled to 0° C. A mixture of 4-chloroindole (2.5 g, 16.5 mmol) and THF (10 mL) is added to the slurry at 4° C. After the addition is completed, the mixture is stirred for 30 min. Then a mixture of O-mesitylenesulfonylhydroxylamine (3.02 g, 14 mmol) and THF (25 mL) is added slowly at a temperature below 5° C. After the addition is completed, the reaction mixture is allowed to reach room temperature and is subsequently stirred for 3 h. Then the mixture is cooled again to 0° C., and a second aliquot of O-mesitylenesulfonylhydroxylamine (3.02 g, 14 mmol) in THF (25 mL) is added slowly. The mixture is allowed to reach ambient temperature and was subsequently stirred overnight. The reaction mixture is worked up by adding it to water, extracting into ethyl acetate, and drying over sodium sulfate. The crude product (4 g) is obtained after filtration of the drying agent and evaporation of the solvent. The aminated indole (2,2 g) is obtained as a black oil (mixture of starting material and product) after flash chromatography, using toluene as eluent.
Reaction SMILES: CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Si:44]([O:51][CH2:52][C:53]1([CH2:70][O:71][Si:72]([C:75]([CH3:78])([CH3:77])[CH3:76])([CH3:74])[CH3:73])[CH2:69][C:56]2=[CH:57][C:58]3[C:63]([C:64]([C:65](=[O:67])[CH3:66])=[C:55]2[CH2:54]1)=[CH:62][CH:61]=[CH:60][C:59]=3Cl)([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45].CCCCCC.CCOCC.[CH3:90][NH:91][CH3:92]>C1COCC1>[Si:44]([O:51][CH2:52][C:53]1([CH2:70][O:71][Si:72]([C:75]([CH3:78])([CH3:77])[CH3:76])([CH3:74])[CH3:73])[CH2:69][C:56]2=[CH:57][C:58]3[C:63]([C:64]([C:65](=[O:67])[CH3:66])=[C:55]2[CH2:54]1)=[CH:62][CH:61]=[CH:60][C:59]=3[N:91]([CH3:92])[CH3:90])([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45]
Reactant: CC(=O)c1c2c(cc3c(Cl)cccc13)CC(CO[Si](C)(C)C(C)(C)C)(CO[Si](C)(C)C(C)(C)C)C2
Reactant: CNC
Agent: CC(C)Oc1cccc(OC(C)C)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(=O)c1c2c(cc3c(N(C)C)cccc13)CC(CO[Si](C)(C)C(C)(C)C)(CO[Si](C)(C)C(C)(C)C)C2
Yield: 71 %

Procedure:
Follows general procedure (pag. 13): [RuPhos Palladacyle] (0.0013 g, 0.0018 mmol), LHMDS (0.15 mL of a 1.0 M solution in THF, 0.15 mmol), 5c (0.040 g, 0.075 mmol) in THF (0.3 mL), dimethylamine (0.056 mL of a 2.0 M solution in THF, 0.11 mmol). The title compound was isolated (n-hexane/Et2O 8:2, 0.029 g, 71% yield) as a yellow oil.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOC1.Br[CH2:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59]>O1CCCC1.C(OCC)(=O)C.O>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([O:23][CH2:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: C[C@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Reactant: CC(C)(C)OC(=O)CBr
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: C[C@H](OCC(=O)OC(C)(C)C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 72 °C
Reaction time: 0.25 h
Yield: 82.4 %

Procedure:
A solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-triene (55.5 mg, 0.0993 mmol), sodium hydride (95%, 15 mg, 0.594 mmol) and 15-crown-5 (15 mg, 0.0681 mmol) in tetrahydrofuran (1 ml) was stirred at an external temperature of 72° C. for 1 hour, to which t-butyl bromoacetate (0.05 ml, 0.336 mmol) was then added at room temperature and further stirred at an external temperature of 72° C. for 5 hours and 15 minutes. After the reaction mixture was diluted with ethyl acetate, water was added dropwise under ice cooling. After washing with saturated aqueous sodium chloride, the organic layer was dried over anhydrous magnesium sulfate. After evaporation under reduced pressure to remove the solvent, the resulting residue was purified by preparative thin layer chromatography (0.5 mm×1 plate, hexane:ethyl acetate=10:1, developed once) to give the titled compound (55.1 mg, 82%) as a colorless oil.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4](S(O)(=O)=O)=[CH:3][CH:2]=1.[C:12]1([CH3:19])C(C)=CC=C[CH:17]=1.[OH2:20]>>[CH2:1]([C:6]1[C:5](=[O:20])[CH2:4][CH2:3][CH:2]=1)[CH2:11][CH2:17][CH2:12][CH3:19]
Reactant: O
Reactant: Cc1ccccc1C
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Product: CCCCCC1=CCCC1=O
Yield: 96 %

Procedure:
The above prepared mixture (18 parts) was admixed with p-toluenesulfonic acid (0.9 part) and xylene (54 parts) and refluxed for 2 hours, during which by-produced water was eliminated by azeotropic distillation. The reaction mixture was treated as in Example 1 to give 2-n-pentyl-2-cyclopentenone in a yield of 96 %.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[CH3:8][O:9][C:10](=[O:42])[C@@H:11]([NH2:41])[CH2:12][NH:13][C:14]([C:16]1[CH:40]=[C:19]2[C:20](=[O:39])[N:21]([CH2:24][CH2:25][CH:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)[CH2:22][CH2:23][N:18]2[N:17]=1)=[O:15]>C1COCC1>[CH3:8][O:9][C:10](=[O:42])[C@@H:11]([NH:41][C:1](=[O:3])[CH3:2])[CH2:12][NH:13][C:14]([C:16]1[CH:40]=[C:19]2[C:20](=[O:39])[N:21]([CH2:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:30][CH2:31]3)[CH2:22][CH2:23][N:18]2[N:17]=1)=[O:15]
Reactant: COC(=O)[C@@H](N)CNC(=O)c1cc2n(n1)CCN(CCC1CCN(C(=O)OC(C)(C)C)CC1)C2=O
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: COC(=O)[C@H](CNC(=O)c1cc2n(n1)CCN(CCC1CCN(C(=O)OC(C)(C)C)CC1)C2=O)NC(C)=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Acetic anhydride (70 ml, 0.76 mmol), was added to a cooled (0°) solution of 4-3 (350 mg, 0.69 mmol) in 10 ml THF. The resulting solution was allowed to warm to room temperature and stirred for 18 h, then concentrated, and the residue was dissolved in 50 ml ethyl acetate and washed successively with NaHCO3, H2O, 10% KHSO4, H2 O, and brine (25 ml each). The organic layer was dried over Na2 SO4 and evaporated giving a colorless residue which was chromatographed on silica gel with 3% CH3OH/CH2Cl2 to yield 4-4 as a white solid.