Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2]I.[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([O:22][CH:23]=[CH2:24])[C:12]2([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:14][CH2:13]2)=[CH:7][C:6]=1[NH:25][C:26](=[O:41])[C@H:27]([C:34]1[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=1)[C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30]>[Zn].[Cu].C(OCC)C>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([O:22][CH:23]2[CH2:2][CH2:24]2)[C:12]2([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:14][CH2:13]2)=[CH:7][C:6]=1[NH:25][C:26](=[O:41])[C@H:27]([C:34]1[CH:35]=[CH:36][C:37]([Cl:40])=[CH:38][CH:39]=1)[C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30]
Reactant: C=COC(c1ccc(Cl)c(NC(=O)[C@H](c2ccc(Cl)cc2)[C@@H](C)C(F)(F)F)c1)C1(C(=O)OC(C)(C)C)CC1
Reactant: ClCI
Agent: [Cu]
Agent: [Zn]
Solvent: CCOCC
Product: C[C@H]([C@H](C(=O)Nc1cc(C(OC2CC2)C2(C(=O)OC(C)(C)C)CC2)ccc1Cl)c1ccc(Cl)cc1)C(F)(F)F
Reaction time: 8 h

Procedure:
68 mg (0.52 mmol) of zinc/copper pair were taken up in 5 ml of abs. diethyl ether, and 41 μl (0.56 mmol) of chloroiodomethane were added at room temperature. A solution of 200 mg (0.35 mmol) of tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]-amino}phenyl)(vinyloxy)methyl]cyclopropanecarboxylate (as diastereomer mixture) in 10 ml of abs. diethyl ether was then added dropwise to the reaction mixture. The reaction solution was then heated to reflux and stirred overnight. After cooling, the solution was filtered through kieselguhr and the kieselguhr was washed repeatedly with diethyl ether. The filtrate obtained was washed with saturated aqueous sodium bicarbonate solution and with water, dried over magnesium sulphate and concentrated to dryness under reduced pressure. The residue was purified by preparative RP-HPLC (mobile phase methanol/water 80:20, isocratic). This gave 54 mg (27% of theory) of the target compound.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](S(C)=O)[N:3]=1.Cl.[CH:19]([NH:22][C:23](=[O:32])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH2:31])=[CH:26][CH:25]=1)([CH3:21])[CH3:20].C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([NH:31][CH2:30][C:27]2[CH:26]=[CH:25][C:24]([C:23]([NH:22][CH:19]([CH3:21])[CH3:20])=[O:32])=[CH:29][CH:28]=2)[C:5]([C:13]#[N:14])=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1C#N
Reactant: CC(C)NC(=O)c1ccc(CN)cc1
Agent: Cl
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)NC(=O)c1ccc(CNc2nc(N)nc(-c3ccco3)c2C#N)cc1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, p-aminomethyl-benzoic acid isopropylamide hydrochloride and DBU in DME. ES-MS m/e (%): 377 (M+H+, 100).
Reaction SMILES: [C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][C:18]=2[CH3:23])[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCCC1.C(O)C.O>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][C:18]=2[CH3:23])[C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C(OC(C)(C)C)c1c(C)cc2c(C)cccc2c1-c1ccc(Cl)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: Cc1cc2c(C)cccc2c(-c2ccc(Cl)cc2)c1C(OC(C)(C)C)C(=O)O
Temperature: 50 °C
Yield: 56.4 %

Procedure:
To a solution of ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3,5-dimethylnaphthalen-2-yl)acetate (32 mg, 0.075 mmol) in tetrahydrofuran: ethanol:water (2:2:1, 3 mL) was added lithium hydroxide (9 mg, 0.377 mmol) and the reaction was heated to 50° C. overnight. The reaction was purified by reverse phase HPLC (Gemini, 40-100% ACN/H2O+0.1% TFA). The product was lyophilized to give a white powder (16.8 mg). 1H-NMR: 400 MHz, (CD3OD) δ: 7.86 (s, 1H), 7.54 (m, 3H), 7.29 (m, 2H), 7.16 (t, J=8.8 Hz, 1H), 7.08 (d, J=8.8 Hz, 1H), 5.17 (s, 1H), 2.69 (s, 3H), 2.65 (s, 3H), 0.98 (s, 9H). LCMS-ESI− (m/z): [M−H]− calcd for C24H24ClO3: 395.15; found: 394.97.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH2:12]([OH:16])[CH:13]([OH:15])[CH3:14].C(N(CC)CC)C>ClCCl.C(OCC)C.CNC>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:16][CH2:12][CH:13]([OH:15])[CH3:14])(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(O)CO
Agent: CNC
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: Cc1ccc(S(=O)(=O)OCC(C)O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97 %

Procedure:
p-Toluenesulphonyl chloride (19.4 g, 102 mmol) was added to a stirred solution of propane-1,2-diol (30 ml), triethylamine (15 ml, 106 mmol), N,N-dimethylamine (108 mg, 0.87 mmol) in dichloromethane (100 ml) at +5° C. The mixture was stirred for 2 hours at +5° C. and overnight at room temperature then diluted with diethyl ether (300 ml) and washed 2M aqueous hydrochloric acid, water (twice) and brine. The combined organic extracts were dried (Na2SO4) and concentrated to give the title compound (22.8 g, 97%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].[Si:23]([O:30][CH2:31][CH:32]([CH2:39][O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH2:33]OS(C)(=O)=O)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C)C=O.O>[Si:23]([O:30][CH2:31][CH:32]([CH2:39][O:40][Si:41]([C:44]([CH3:45])([CH3:47])[CH3:46])([CH3:42])[CH3:43])[CH2:33][O:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[CH:6][C:3]=1[CH:4]=[O:5])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]
Reactant: COc1cc(O)c(C=O)cc1-c1cccs1
Reactant: CC(C)(C)[Si](C)(C)OCC(CO[Si](C)(C)C(C)(C)C)COS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(OCC(CO[Si](C)(C)C(C)(C)C)CO[Si](C)(C)C(C)(C)C)c(C=O)cc1-c1cccs1
Temperature: 80 °C
Reaction time: 1 h
Yield: 329.3 %

Procedure:
Ex-13D: To a solution of 2-hydroxy-4-methoxy-5-thien-2-ylbenzaldehyde (Ex-13C, 0.10 g, 0.43 mmol) in N,N-dimethylformamide (3 mL) was added potassium carbonate (0.18 g, 1.3 mmol) and the resulting yellow slurry was heated to 80° C. Methanesulfonic acid 3-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)propyl ester (Ex-13A, 0.24 g, 1.3 mmol) was then added dropwise in three equal portions with stirring at 1 h intervals. After the last addition, the reaction was stirred for an additional 1 h at 80° C. and cooled to room temperature. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was sequentially washed with a saturated ammonium chloride solution (15 mL), water (15 mL), and brine (15 mL), dried over sodium sulfate, and concentrated to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 1:6) gave 0.78 g (90%) of 2-[3-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)propoxy]-4-methoxy-5-thien-2-ylbenzaldehyde as a pale green solid, mp 91–92° C. 1H-NMR (300 MHz, CDCl3) δ 10.34 (s, 1H), 8.13 (s, 1H), 7.41 (dd, 1H, J=3.6, 1.2 Hz), 7.28 (dd, 1H, J=5.1, 1.2 Hz), 7.05 (dd, 1H, J=5.1, 3.6 Hz), 6.54 (s, 1H), 4.22 (d, 2H, J=5.7 Hz), 3.96 (s, 3H), 3.80 (d, 4H, J=5.7 Hz), 2.33 (pentet, 1H, J=5.7 Hz), 0.88 (s, 18H), 0.012 (s, 12H). HRMS (EI) Calcd. for C28H46O5SSi2: 550.2604 (M+); Found: 550.2593.
Reaction SMILES: [OH:1][C@H:2]([CH3:6])[C:3]([NH2:5])=O.F[B-](F)(F)F.C([O+](CC)CC)C.N[C:20]1[C:21]([NH:29][C@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)=[C:22]2[S:28][CH:27]=[CH:26][C:23]2=[N:24][CH:25]=1>O1CCCC1.C(O)C>[OH:1][C@@H:2]([C:3]1[N:29]([C@H:30]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]2)[C:21]2=[C:22]3[S:28][CH:27]=[CH:26][C:23]3=[N:24][CH:25]=[C:20]2[N:5]=1)[CH3:6]
Reactant: C[C@@H](O)C(N)=O
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](Nc2c(N)cnc3ccsc23)C1
Agent: CC[O+](CC)CC
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CCCN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1.25 h
Yield: 90 %

Procedure:
A mixture of (2R)-2-hydroxypropanamide (197 mg, 2.21 mmol) and triethyloxonium tetrafluoroborate (395 mg, 2.08 mmol) in tetrahydrofuran (4.0 mL) was stirred at room temperature for 75 min then concentrated. The residue was dissolved in ethanol (1.5 mL) and this solution was then added to a solution of tert-butyl (3S)-3-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]piperidine-1-carboxylate (0.24 g, 0.69 mmol) in ethanol (3.5 mL) in a vial. The resulting mixture was stirred at 80° C. for 2 h. The solvent was evaporated and the crude purified on silica gel, eluted with 0-10% MeOH in dichloromethane to give 250 mg (86%) of the desired product. LCMS calculated for C20H27N4O3S (M+H)+: m/z=403.2. Found: 403.1.
Reaction SMILES: [Na].CC(C)=O.Cl.[C:7]([NH2:13])(=[NH:12])[CH2:8][CH2:9][CH2:10][CH3:11].[N+:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]=[C:24]=[O:25])([O-:16])=[O:15]>C1C=CC=CC=1>[N+:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[NH:23][C:24]([NH:12][C:7](=[NH:13])[CH2:8][CH2:9][CH2:10][CH3:11])=[O:25])([O-:16])=[O:15]
Reactant: CCCCC(=N)N
Reactant: O=C=Nc1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: [Na]
Solvent: CC(C)=O
Solvent: c1ccccc1
Product: CCCCC(=N)NC(=O)Nc1ccccc1[N+](=O)[O-]

Procedure:
Following a procedure similar to that described in Example 1 but using 2.3 g. sodium in 150 ml. dry acetone, 13.6 g. valeramidine hydrochloride, and 16.4 g. 2-nitrophenyl isocyanate in 300 ml. benzene, there was obtained after recrystallization from ethyl alcohol 9.1 g. of the hydrochloride of 1-(2-nitrophenyl)-3-(pentanimidoyl)urea; m.p. 130°-132°C.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[CH:33]=[CH:32][C:17]2[C:18]([CH:21]3[CH2:26][CH2:25][N:24]([CH:27]([CH2:30][CH3:31])[CH2:28]O)[CH2:23][CH2:22]3)=[N:19][O:20][C:16]=2[CH:15]=1.[C:34]1(=[O:44])[NH:38][C:37](=[O:39])[C:36]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOCC>[F:13][C:14]1[CH:33]=[CH:32][C:17]2[C:18]([CH:21]3[CH2:26][CH2:25][N:24]([CH:27]([CH2:30][CH3:31])[CH2:28][N:38]4[C:37](=[O:39])[C:36]5=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]5[C:34]4=[O:44])[CH2:23][CH2:22]3)=[N:19][O:20][C:16]=2[CH:15]=1
Reactant: CCC(CO)N1CCC(c2noc3cc(F)ccc23)CC1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCC(CN1C(=O)c2ccccc2C1=O)N1CCC(c2noc3cc(F)ccc23)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 7.6 %

Procedure:
A solution of diethyl azodicarboxylate (DEAD, 4.9 g, 28.3 mmol) in THF (50 ml) was added dropwise to a solution of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]butanol (6.9 g, 23.6 mmol), phthalimide (4.16 g, 1.2 eq), and triphenylphosphine (7.4 g, 28.3 mmol) in THF (200 ml) at room temperature. The solution was stirred at room temperature for 24 hours. After the reaction, the solvent was stripped to dryness. The residue was stirred in ether (200 ml) and the insolubles were removed by filtration. The oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g, eluted with dichloromethane, DCM, and 1-2% CH3OH in DCM) and (100 g of SiO2 ; eluted with DCM, 1l, and 1% CH3OH in DCM, 1.2 l). Two close compounds were separated and the top compound on TLC (1.6 g) was recrystallized from isopropyl ether to yield 0.76 g of white crystals, m.p. 86°-88° C.
Reaction SMILES: [CH:1]1[C:14]2[CH:13]=[C:12](B(O)O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:18]1([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:23]=[CH:22][CH:21]=[C:20]([C:24]2[N:29]=[C:28]([C:30]3[CH:31]=[C:32]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH:33]=[CH:34][CH:35]=3)[N:27]=[C:26]([C:42]3[CH:47]=[C:46](Br)[CH:45]=[C:44](Br)[CH:43]=3)[N:25]=2)[CH:19]=1.C([O-])([O-])=O.[K+].[K+].[N:62]1[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=1[C:68]1[CH:73]=[CH:72][C:71](B(O)O)=[CH:70][CH:69]=1>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.C(O)C.C1(C)C=CC=CC=1>[C:18]1([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:23]=[CH:22][CH:21]=[C:20]([C:24]2[N:29]=[C:28]([C:30]3[CH:31]=[C:32]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH:33]=[CH:34][CH:35]=3)[N:27]=[C:26]([C:42]3[CH:47]=[C:46]([C:71]4[CH:70]=[CH:69][C:68]([C:63]5[CH:64]=[CH:65][CH:66]=[CH:67][N:62]=5)=[CH:73][CH:72]=4)[CH:45]=[C:44]([C:13]4[C:14]5[C:5]([C:6]6[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=6[CH:12]=4)=[CH:4][CH:3]=[CH:2][CH:1]=5)[CH:43]=3)[N:25]=2)[CH:19]=1
Reactant: OB(O)c1ccc(-c2ccccn2)cc1
Reactant: Brc1cc(Br)cc(-c2nc(-c3cccc(-c4ccccc4)c3)nc(-c3cccc(-c4ccccc4)c3)n2)c1
Reactant: OB(O)c1cc2ccccc2c2ccccc12
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: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: c1ccc(-c2cccc(-c3nc(-c4cccc(-c5ccccc5)c4)nc(-c4cc(-c5ccc(-c6ccccn6)cc5)cc(-c5cc6ccccc6c6ccccc56)c4)n3)c2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 58 %

Procedure:
In a stream of argon, 0.54 g (2.42 mmol) of 9-phenanthreneboronic acid, 1.50 g (2.42 mmol) of 4,6-bis(biphenyl-3-yl)-2-(3,5-dibromophenyl)-1,3,5-triazine and 56.0 mg (0.048 mmol) of tetrakis(triphenylphosphine)palladium were suspended in a mixed solvent composed of 150 mL of toluene and 20 mL of ethanol, and the resultant suspension was heated to 60° C. To the suspension, 7.26 mL (7.26 mmol) of an aqueous 1M K2CO3 solution was gradually added dropwise, and the mixture was stirred for 3 hours. Then the mixture was cooled to room temperature, and 0.72 g (3.63 mmol) of 4-(2-pyridyl)phenylboronic acid and 7.26 mL (7.26 mmol) of an aqueous 1M K2CO3 solution were added. Then the mixture was heated to 60° C. and maintained at that temperature for 4 hours while being stirred. Then the reaction mixture was cooled to room temperature, and was then distilled under a reduced pressure to remove all volatile materials. Methanol was added to the concentrate, and the thus-deposited solid was collected by filtration. The obtained crude product was purified by silica gel chromatography using a hexane/chloroform (1:2) mixed solvent as an eluent to give 1.1 g of the target 4,6-bis(biphenyl-3-yl)-2-[5-(9-phenathryl)-4′-(2-pyridyl)biphenyl-3-yl]-1,3,5-triazine as a white solid (yield: 58%).
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([NH:11][C:12]3[C:13]4[C:20]([C:21]([OH:23])=O)=[CH:19][NH:18][C:14]=4[N:15]=[CH:16][N:17]=3)=[CH:10][C:4]=2[S:3]1.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC.C(N(C(C)C)C(C)C)C.[OH-].[Na+]>O.CN(C)C=O>[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([C:21]([C:20]2[C:13]3[C:12]([NH:11][C:9]4[CH:8]=[CH:7][C:5]5[NH:6][C:2](=[O:1])[S:3][C:4]=5[CH:10]=4)=[N:17][CH:16]=[N:15][C:14]=3[NH:18][CH:19]=2)=[O:23])[CH2:27][CH2:26]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1c[nH]c2ncnc(Nc3ccc4[nH]c(=O)sc4c3)c12
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: CN1CCN(C(=O)c2c[nH]c3ncnc(Nc4ccc5[nH]c(=O)sc5c4)c23)CC1
Yield: 46.7 %

Procedure:
A mixture comprising 18.7 mg (57 μmol) 4-[(2-Oxo-2,3-dihydro-1,3-benzothiazol-6-yl)amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (prepared according to example 3), 0.64 mL N,N-dimethylformamide, 57.2 mg 1-methylpiperazine, 136 μL 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide solution (50% in ethyl acetate) and 29.9 μL N-ethyl-N-isopropylpropan-2-amine was stirred at 23° C. for 2 days. Water was added, the solution was neutralized by addition of sodium hydroxide solution, the solvents were removed and the residue purified by chromatography to give 10.9 mg (44%) of the title compound.
Reaction SMILES: [C:1]1([NH:7][C:8]2[C:16]3[C:15]4[CH2:17][NH:18][CH2:19][CH2:20][C:14]=4[NH:13][C:12]=3[N:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:21][C:22]1[CH:23]=[C:24]([S:28](Cl)(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1.C(N(CC)CC)C>ClCCCl>[Cl:21][C:22]1[CH:23]=[C:24]([S:28]([N:18]2[CH2:19][CH2:20][C:14]3[NH:13][C:12]4[N:11]=[CH:10][CH:9]=[C:8]([NH:7][C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:16]=4[C:15]=3[CH2:17]2)(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc(Nc2ccnc3[nH]c4c(c23)CNCC4)cc1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(c1cccc(Cl)c1)N1CCc2[nH]c3nccc(Nc4ccccc4)c3c2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 22.8 %

Procedure:
Phenyl-(6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;3′,4′-d]pyrrol-4-yl)-amine (40 mg, 0.15 mmol), 3-chlorophenylsulfonyl chloride (38 mg, 0.18 mmol), and triethylamine (0.06 mL, 0.45 mmol) were dissolved in 1,2-dichloroethane (2.0 mL), and stirred overnight at room temperature. The reaction mixture was added directly to a Biotage column. The crude product was purified via Biotage eluting with CH2Cl2/MeOH (9/1, v/v) to provide 11 (15 mg, 23% yield) as a brown solid. LC-MS (M+H=439, obsd.=439).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:10]=1[CH2:11][N:12]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=1)[CH2:13][CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:28]=[N+:29]=[N-:30].[Na+].[Cl-].[NH4+].O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:10]=1[CH2:11][N:12]([C:15]1[CH:16]=[CH:17][C:18]([C:19]2[NH:30][N:29]=[N:28][N:20]=2)=[CH:21][CH:22]=1)[CH2:13][CH3:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [N-]=[N+]=[N-]
Reactant: CCN(Cc1cc(Br)ccc1OCc1ccccc1)c1ccc(C#N)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCN(Cc1cc(Br)ccc1OCc1ccccc1)c1ccc(-c2nnn[nH]2)cc1
Temperature: 120 °C
Reaction time: 18 h

Procedure:
A mixture of 4-[N-(2-benzyloxy-5-bromobenzyl)-N-ethyl-amino]benzonitrile (3.79 g), sodium azide (0.9 g) and ammonium chloride (1.4 g) in N,N-dimethylformamide (30 mL) was heated and stirred at 120° C. for 18 hours. The reaction mixture was allowed to cool and was poured into water (100 mL). The precipitate was filtered and dried. On crystallization from acetic acid there was obtained 5-[4-[N-(2- benzyloxy-5-bromobenzyl)-N-ethylamino)phenyl]tetrazole, yield 1.2 g, mp 206°-208° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[CH:14]=[C:13](Cl)[N:12]=[CH:11][N:10]=2)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:22][C:23]([F:33])([F:32])[C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27][NH2:28]>CN(C)C=O>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[C:9]1[N:10]=[CH:11][N:12]=[C:13]([NH:28][CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([C:23]([F:22])([F:32])[F:33])[CH:25]=2)[CH:14]=1
Reactant: Nc1ccc(Cl)cc1-c1cc(Cl)ncn1
Reactant: NCc1cccc(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1ccc(Cl)cc1-c1cc(NCc2cccc(C(F)(F)F)c2)ncn1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
Into a 50-mL round bottom flask, was placed a solution of 4-chloro-2-(6-chloropyrimidin-4-yl)benzenamine (1.5 g, 6.25 mmol, 1.00 equiv) in N,N-dimethylformamide (30 mL), potassium carbonate (2.7 g, 19.54 mmol, 3.00 equiv), 3-(trifluoromethyl)benzylamine (1.7 g, 9.70 mmol, 1.50 equiv). The resulting solution was stirred overnight at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 20 mL of ethyl acetate. The resulting mixture was washed with 2×20 mL of water. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 1 g (42%) of N-(3-(trifluoromethyl)benzyl)-6-(2-amino-5-chlorophenyl)pyrimidin-4-amine as yellow oil
Reaction SMILES: B.O1CCCC1.[Br:7][C:8]1[CH:13]=[C:12]([C:14]#[N:15])[CH:11]=[CH:10][C:9]=1[O:16][CH3:17]>O1CCCC1>[NH3:15].[Br:7][C:8]1[CH:13]=[C:12]([CH2:14][NH2:15])[CH:11]=[CH:10][C:9]=1[O:16][CH3:17]
Reactant: COc1ccc(C#N)cc1Br
Agent: B
Solvent: C1CCOC1
Product: COc1ccc(CN)cc1Br
Product: N
Temperature: -10 °C
Yield: 142 %

Procedure:
Borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran. 250 ml) was added to a solution of 2-bromo-4-cyanoanisole (17 g) in tetrahydrofuran (150 ml). The mixture was heated at reflux for 2 hours then cooled to -10° C. and carefully quenched with 6N HCl (130 ml). The mixture was basified with 4N NaOH then extracted with ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography, eluting with 120:8:1 dichloromethane:methanol:ammonia, to give the title compound (12.3 g, 71%); δH (250MHz, CDCl3) 3.80 (2H, s, CH2NH2), 3.92 (3H, s, ArOCH3), 6.85 (1H, d, J 8.4Hz, 6-H), 7.20 (1H, dd, J 8.4, 2.1Hz, 5-H), 7.51 (1H, d, J 2.1Hz, 3-H).
Reaction SMILES: [C:1]([OH:20])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12]CCCCCC.[CH2:21]([OH:39])[CH2:22][CH2:23]CCCCC/C=C\CCCCCCCC.[CH2:40](O)CCCCCCCCCCC=CCC.C(N)(=O)CCCCCCC/C=C\CCCCCCCC>>[C:21]([O:20][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])(=[O:39])[C:22]([CH3:40])=[CH2:23]
Reactant: CCC=CCCCCCCCCCCCO
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CCCCCCCC/C=C\CCCCCCCCO
Agent: CCCCCCCC/C=C\CCCCCCCC(N)=O
Product: C=C(C)C(=O)OCCCCCCCCCCCC

Procedure:
Acrylated castor oil; Acrylated ricinoleic acid; Methacrylated ricinoleic acid; Soya Bean Oil; Unsaturated fatty acids, e.g. Oleic acid, tallow fatty acid; Unsaturated fatty alcohols, e.g. Oleyl alcohol, pentadeca-12-ene-1-ol.; Oleamide; Triglycerides, e.g. tall oil, ting oil; Ethylenic unsaturated urethanes; Acrylic unsaturated urethanes; Air drying short oil alkyds; Alkyl and Aryl Esters of maleic anhydride, singly or in combination.
Reaction SMILES: [CH:1]([NH:4][C:5](=[O:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1)([CH3:3])[CH3:2].[CH:15]([Sn](CCCC)(CCCC)CCCC)=[CH2:16]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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:1]([NH:4][C:5](=[O:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH:15]=[CH2:16])=[CH:9][CH:8]=1)([CH3:3])[CH3:2]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: CC(C)NC(=O)Cc1ccc(Br)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: C=Cc1ccc(CC(=O)NC(C)C)cc1
Yield: 72.8 %

Procedure:
N-Isopropyl-4-bromophenylacetamide (1.0 g) and vinyltributyltin (1.4 ml) were dissolved in toluene (12 ml). After adding tetrakistriphenylphosphinepalladium (0.5 g) thereto, the resultant mixture was heated under reflux for 4 hr. Then it was allowed to cool and diluted with ethyl acetate. The resulting solid was filtered off and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate system) to give colorless crystals (0.578 g) of the title compound (yield: 72.8%).