Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[C:6]2[C:7]([O:11][CH3:12])=[N:8][CH:9]=[CH:10][C:5]=2[N:4]([CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][C:30]([S:33]([NH2:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.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>[CH3:12][O:11][C:7]1[C:6]2[C:2]([C:27]3[CH:32]=[CH:31][C:30]([S:33]([NH2:36])(=[O:35])=[O:34])=[CH:29][CH:28]=3)=[CH:3][N:4]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:5]=2[CH:10]=[CH:9][N:8]=1
Reactant: CC1(C)OB(c2ccc(S(N)(=O)=O)cc2)OC1(C)C
Reactant: COc1nccc2c1c(I)cn2C1CCOCC1
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: O
Solvent: CN(C)C=O
Product: COc1nccc2c1c(-c1ccc(S(N)(=O)=O)cc1)cn2C1CCOCC1
Temperature: 130 °C
Reaction time: 1 h
Yield: 42.3 %

Procedure:
To a solution of 3-iodo-4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridine (50.0 mg) in DMF (2 mL)/water (0.20 mL) were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (59.0 mg), tetrakis(triphenylphosphine)palladium(0) (16.0 mg) and potassium carbonate (39.2 mg). The reaction mixture was stirred under microwave irradiation at 130° C. for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica, gel column chromatography (hexane/ethyl acetate) to give the title compound (22.9 mg).
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]([F:43])([F:42])[C:10]1[CH:11]=[C:12]([C@H:20]2[O:24][C:23](=[O:25])[N:22]([CH2:26][C:27]#[C:28][C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[C@H:21]2[CH3:41])[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1.[OH:44][N:45]=[C:46](Cl)[CH3:47]>C1(C)C=CC=CC=1.Cl>[F:43][C:9]([F:8])([F:42])[C:10]1[CH:11]=[C:12]([C@H:20]2[O:24][C:23](=[O:25])[N:22]([CH2:26][C:27]3[C:46]([CH3:47])=[N:45][O:44][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[C@H:21]2[CH3:41])[CH:13]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:15]=1
Reactant: CC(Cl)=NO
Reactant: COc1cc(F)c(C(C)C)cc1C#CCN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc(F)c(C(C)C)cc1-c1onc(C)c1CN1C(=O)O[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
Temperature: 25 °C

Procedure:
Triethylamine (123.4 mg, 170 μL, 1.21 mmol) was added to a stirred solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one (21.9 mg, 0.0423 mmol) and N-hydroxyethanimidoyl chloride (124.4 mg, 1.33 mmol) in dry toluene (2 mL) at room temperature under N2. The reaction was heated at reflux for 2 days. The reaction mixture was cooled to room temperature, diluted with 1N HCl and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(4-fluoro-5-isopropyl-2-methoxyphenyl)-3-methylisoxazol-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.38 (20% EtOAc/hexanes). LCMS calc.=575.2; found=575.3 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 7.84 (s, 1H); 7.64 (s, 2H); 7.31 (d, J=8.3 Hz, 1H); 6.68 (d, J=11.8 Hz, 1H); 5.27 (d, J=8.0 Hz, 1H); 4.78 (d, J=15.6 Hz, 1H); 4.00 (d, J=15.6 Hz, 1H); 3.82 (s, 3H); 3.72-3.68 (m, 1H); 3.22-3.16 (m, 1H); 2.38 (s, 3H); 1.24 (d, J=7.0 Hz, 3H); 1.22 (d, J=7.0 Hz, 3H); 0.42 (d, J=6.6 Hz, 3H).
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15](=O)[CH3:16])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[NH2:18][CH2:19][CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=1)[OH:21].C1C=CC=CC=1.C([BH3-])#N.[Na+]>C(O)(C)C>[C:1]([O:4][CH2:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH:15]([NH:18][CH2:19][CH:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[OH:21])[CH3:16])=[CH:11][CH:12]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)COc1ccc(CCOC(C)=O)cc1
Reactant: NCC(O)c1cccc(Cl)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CC(C)O
Product: CC(=O)OCCc1ccc(OCC(C)NCC(O)c2cccc(Cl)c2)cc1
Yield: 14.8 %

Procedure:
Following a procedure similar to that described in Example 6, but using 2 g of 2-[4-(2-oxopropoxy)phenyl]ethyl acetate (prepared as described in Preparation 37), 1.45 g of 2-amino-1-(3-chlorophenyl)ethanol (prepared as described in Preparation 8), 60 ml of dry benzene, 50 ml of absolute isopropanol and 2.06 g of sodium cyanoborohydride, and then purifying the reaction product by column chromatography through silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as the eluent, 0.49 g of the title compound was obtained, having an Rf=0.34 (thin layer chromatography over silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as the developing solvent).
Reaction SMILES: [C:1]([CH:9]=[CH:10][C:11]([O:13]CC)=[O:12])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:16][C@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:18]1=[O:36].C(O)(=O)C>C1(C)C=CC=CC=1.[Pd]>[C:11]([CH:10]([NH:16][CH:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:28][C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[C:18]1=[O:36])[CH2:9][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([OH:13])=[O:12]
Reactant: CC(C)(C)OC(=O)CN1C(=O)[C@@H](N)CCc2ccccc21
Reactant: CCOC(=O)C=CC(=O)c1ccccc1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)CN1C(=O)C(NC(CCc2ccccc2)C(=O)O)CCc2ccccc21
Reaction time: 18 h
Yield: 56.7 %

Procedure:
Ethyl 3-benzoylacrylate (13a) (55.6 g, 272 mmoles) is dropped into a solution of (3S)-3-amino-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (11) (66.2 g, 228 mmoles) in 200 ml of toluene, at room temperature in 1 h. The resulting mixture is left under stirring for 18 h, added with 10% Pd—C (26 g, 22 mmoles) and hydrogenated at 3 atm for 18 h at room temperature. After completion of the reaction, 200 ml of acetic acid are added and the mixture is hydrogenated for a further 18 h, at 3 atm at room temperature, after that the catalyst is filtered off through Celite and the solvent mixture is evaporated to dryness. The residue is taken up with isopropanol (500 ml) and the resulting precipitate is filtered, washed with 20 ml of dichloromethane and dried to give 3-[[1-(carboxy)-3-phenyl-propyl]amino]-1-t-butoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepin-2-one (15) (58.5 g, yield: 52%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:6]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:5]1=2.[C:25]1([N:31]=[C:32]=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1>[NH:31]([C:32]([NH:1][CH2:2][CH2:3][N:4]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:6]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:5]1=2)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CC(C)(C)OC(=O)N1CCc2c(n(CCN)c3ccccc23)CC1
Reactant: O=C=Nc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCc2c(n(CCNC(=O)Nc3ccccc3)c3ccccc23)CC1
Reaction time: 2.5 h
Yield: 71.9 %

Procedure:
tert-Butyl 6-(2-aminoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.0399 g, 0.121 mmol) was dissolved in THF (2 mL) at rt under N2. Phenyl isocyanate (0.016 g mL, 0.0173 g, 0.145 mmol, 1.20equiv.) was added, then the reaction mixture was stirred for 2.5 h. The reaction mixture was concentrated and the crude product (0.0598 g) was chromatographed (SiO2 25 g, eluted with 3:2 hexane:EtOAc) to give tert-butyl 6-{2-[(anilinocarbonyl)amino]ethyl}-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.0390 g) in 72% yield. 1H NMR (300 MHz, CDCl3) δ 1.36, 1.44, 2.96-3.08, 3.42-3.51, 3.65-3.72, 4.17, 4.23, 5.14, 5.23, 6.94-7.30, 7.43-7.49; MS (ESI+) for C26H32N4O3 m/z 449.1 (M+H)+.
Reaction SMILES: N1C=C2C(N=CN2)=NC=1.[Cl:10][C:11]1[N:19]=[C:18]2[C:14]([NH:15][CH:16]=[N:17]2)=[C:13]([Cl:20])[N:12]=1.[CH3:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(N(CC)CC)C>ClCCl>[Cl:10][C:11]1[N:19]=[C:18]2[C:14]([N:15]=[CH:16][N:17]2[C:25]2[CH:26]=[CH:27][C:22]([CH3:21])=[CH:23][CH:24]=2)=[C:13]([Cl:20])[N:12]=1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Reactant: Cc1ccc(B(O)O)cc1
Agent: c1ncc2[nH]cnc2n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(-n2cnc3c(Cl)nc(Cl)nc32)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 46 %

Procedure:
Purine N9 arylation via boronic acids/cupric acetate: A 20 mL glass vial equipped with a magnetic stir bar was charged with 2,6-dichloropurine (0.200 g, 1.06 mmol, 1.0 equiv), 4-methylphenylboronic acid (0.288 g, 2.12 mmol, 2.0 equiv), anhydrous cupric acetate (0.384 g, 2.12 mmol, 2.0 equiv.), 4 Å activated molecular sieves (0.500 g), triethylamine (0.443 mL, 3.18 mmol, 3.0 equiv.) and dichloromethane (5.0 mL). The reaction was stirred under air at ambient temperature and monitored by TLC. When the reaction was complete after 24 hours, it was filtered through Celite, washed with methanol and purified by flash column chromatography (1% methanol in dichloromethane) to afford desired 2,6-dichloro-9-(4-methylphenyl)-purine (0.136 g, 47%). 1H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 7.41 (d, 2H, J=8.1 Hz), 7.54 (d, 2H, J=8.1 Hz), 8.35 (s, 1H); HRMS (MALDI-FTMS) C12H8Cl2N4 [MH+] 279.0199, found: 279.0208.
Reaction SMILES: [NH2:1][C@@H:2]([C:6]([OH:8])=[O:7])[C@H:3]([CH3:5])[OH:4].C([O-])(O)=O.[Na+].[C:14](=O)([O-:34])[O:15][CH:16](C1C=CC=CN=1)C1C=CC(C2C=CSC=2)=CC=1.[S:36]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44](C3C=CN(C([O-])=O)C(=O)C=3C)=[CH:43][CH:42]=2)=[CH:37]1>O.C1COCC1>[OH:4][C@@H:3]([CH3:5])[C@@H:2]([N:1]([C:44]1[CH:43]=[CH:42][C:41]([C:38]2[CH:39]=[CH:40][S:36][CH:37]=2)=[CH:46][CH:45]=1)[C:14]([O:15][CH3:16])=[O:34])[C:6]([OH:8])=[O:7]
Reactant: C[C@H](O)[C@@H](N)C(=O)O
Reactant: Cc1c(-c2ccc(-c3ccsc3)cc2)ccn(C(=O)[O-])c1=O
Reactant: O=C([O-])OC(c1ccc(-c2ccsc2)cc1)c1ccccn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)N(c1ccc(-c2ccsc2)cc1)[C@@H](C(=O)O)[C@H](C)O
Reaction time: 15 h

Procedure:
To a stirred mixture of D-threonine (0.067 g, 0.56 mmol) and NaHCO3 (0.07 g, 0.84 mmol) in H2O (3.0 mL), the crude mixture containing 2-pyridyl-[4-(3-thienyl)-phenyl]-methyl carbonate and [4-(3-thienyl)-phenyl]-methyl-2-oxopyridine-1-carboxylate (0.263 g, 0.84 mmol) in THF (3.0 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×5 mL). The aqueous phase was acidified with 2.0 M HCl solution to pH 2-3 and subsequently extracted with EtOAc (3×10 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.188 g, quant.) as white solid, which was used in the next step without further purification. MS (ESI) m/z: 353 [M−NH4]+. 1H NMR (DMSO-d6) δ: 1.10 (d, J=6.4 Hz, 3H), 3.97 (dd, J=3.5, 8.9 Hz, 1H), 4.08 (dq, J=3.5, 6.4 Hz, 1H), 5.07 (s, 2H), 6.96 (d, J=8.9 Hz, 1H), 7.41 (d, J=8.1 Hz, 2H), 7.53-7.60 (m, 1H), 7.64 (dd, J=2.9, 5.0 Hz, 1H), 7.72 (d, J=8.1 Hz, 2H), 7.86-7.91 (m, 1H), 12.58 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4]([F:22])[CH:3]=1.[S:23](Cl)([Cl:26])(=[O:25])=[O:24].N1C=CC=CC=1>C(Cl)Cl>[S:23]([Cl:26])([O:8][C:7]1[CH:6]=[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:17])[F:19])[N:11]([CH3:20])[C:10]2=[O:21])[C:4]([F:22])=[CH:3][C:2]=1[Cl:1])(=[O:25])=[O:24]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(O)c(Cl)cc2F)c1=O
Reactant: O=S(=O)(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(OS(=O)(=O)Cl)c(Cl)cc2F)c1=O

Procedure:
A solution of 10.16 g of 3-(4-chloro-2-fluoro-5 -hydroxyphenyl)-1-methyl-6 -trifluoromethyl-2,4 (1H,3H)-pyrimidinedione and 20.20 g of sulphuryl chloride in 100 ml of methylene chloride is treated with a solution of 3.56 g of pyridine in 10 ml of methylene chloride while stirring and cooling during 5 minutes. The temperature rises to 20° C. The reaction mixture is stirred at 20°-25° C. for 15 minutes, subsequently poured on to ice and stirred vigorously. The organic phase is washed throughly with water, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. There is obtained 2-chloro-5-[3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1(2H)-pyrimidinyl]-4-fluorophenyl chlorosulphate m.p. 133°-135° C.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][N:10]2[C:13]([C:16]([OH:18])=O)=[CH:14][N:15]=[C:9]2[CH:8]=1)=[O:6])[CH3:3].C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH2:38]([C:40]1[C:48]2[C:47]([NH2:49])=[CH:46][CH:45]=[CH:44][C:43]=2[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([CH3:57])[N:52]=2)[N:41]=1)[CH3:39]>CN1C(=O)CCC1>[CH2:38]([C:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][C:47]=2[NH:49][C:16]([C:13]2[N:10]3[CH:11]=[CH:12][C:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])=[CH:8][C:9]3=[N:15][CH:14]=2)=[O:18])[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([CH3:57])[N:52]=2)[N:41]=1)[CH3:39]
Reactant: CCc1nn(Cc2cccc(C)n2)c2cccc(N)c12
Reactant: CCOC(=O)c1ccn2c(C(=O)O)cnc2c1
Agent: Cl
Agent: O=C(Cl)c1c(Cl)cc(Cl)cc1Cl
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccn2c(C(=O)Nc3cccc4c3c(CC)nn4Cc3cccc(C)n3)cnc2c1
Temperature: 75 °C
Reaction time: 0.5 h
Yield: 82.5 %

Procedure:
To 7-(ethoxycarbonyl) imidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride (501 mg, 1.85 mmol) in NMP (10 mL) was added triethylamine (468 mg, 4.63 mmol). The suspension turned into a clear solution. 2,4,6-trichlorobenzoyl chloride (474 mg, 1.94 mmol) was added dropwise to the reaction mixture. A milky suspension resulted after 10 minutes. The mixture was stirred for another 30 minutes. 3-Ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (444 mg, 1.67 mmol) was added in one portion to the reaction mixture. The mixture was sealed and heated to 75° C. for 3 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure to remove NMP. The residue was diluted with EtOAc/H2O (20 mL/10 mL). The organic phase was washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. Silica gel chromatography (EtOAc/Hexane 5:1 to 10:1) provided the final product (665 mg). MS (ES+APCI) m/z=483 (M+H).
Reaction SMILES: [N+]([O-])([O-])=[O:2].[U+2:5](=[O:7])=[O:6].[N+]([O-])([O-])=O.[N+]([O-])(O)=O.[CH:16]([O-:18])=[O:17].[U+2](=O)=O.[CH:22]([O-:24])=[O:23]>C(O)=O>[OH2:2].[CH:16]([O-:18])=[O:17].[U+2:5](=[O:7])=[O:6].[CH:22]([O-:24])=[O:23]
Reactant: O=[N+]([O-])[O-]
Agent: O=C[O-]
Agent: O=[U+2]=O
Solvent: O=[N+]([O-])O
Solvent: O=CO
Product: O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To demonstrate the feasibility of preparing U3O8 having a controlled particle size distribution, an exemplary feed solution (85 ml) was prepared of uranyl nitrate having a concentration of 250 gU/l at 2 M HNO3. Feed solution was contacted in suitable denitration apparatus with 70 ml of 19.9 M formic acid at a feed rate of 0.70 moles formic acid/(min)(liter of uranyl nitrate feed) solution at a temperature of 90° C. Sufficient formic acid was added to achieve a concentration of 0.3 moles /100 grams of solution at the completion of denitration. The solution was digested for one hour after completion of the formic acid addition to assure complete denitration and formation of an unsaturated solution of uranyl formate. An additional 365 ml of 19.9 M formic acid was added to the unsaturated uranyl formate solution at a feed rate of 1.27 moles/(min)(liter of uranyl nitrate feed) at 90° C. to precipitate uranyl formate monohydrate. To maximize uranium precipitation the formic acid was added until the solution acid concentration reached 1.4 moles/100 g of solution. The solution was evaporated to reduce the solution volume by 60% and adjusted with 75 ml of 90% formic acid. The slurry was cooled to ambient temperature and the precipitate recovered by filtration at a formic acid concentration of 1.7 moles/100 g solution. The precipitate was washed with 90% formic acid and the resulting filter cake was dried at 110° C. for 2 hours to provide crystalline uranyl formate monohydrate salt. This salt was then calcined in a static bed in an air atmosphere at 800° C. for 6 hours. The resulting product was a crystalline free-flowing U3O8 powder having the particle size distribution shown in the FIGURE of the attached drawing.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[C:9]([C:10]([OH:12])=O)[C:8]([NH2:14])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][N:17]=1.[I-].[K+].COCCOCCOCCOC>>[C:22]([C:19]1[CH:20]=[CH:21][C:16]2[N:17]([CH:18]=1)[C:10](=[O:12])[C:9]1[C:8](=[CH:7][CH:6]=[C:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH:13]=1)[N:14]=2)#[N:23]
Reactant: CC(C)Oc1ccc(N)c(C(=O)O)c1
Reactant: N#Cc1ccc(Cl)nc1
Agent: [I-]
Agent: [K+]
Solvent: COCCOCCOCCOC
Product: CC(C)Oc1ccc2nc3ccc(C#N)cn3c(=O)c2c1

Procedure:
A mixture of 16.7 g. of 5-isopropoxyanthranilic acid, 10.0 g. of 2-chloro-5-cyanopyridine and 0.01 g. of potassium iodide in 30 ml. of triglyme was heated to a bath temperature of 150° overnight under a stream of argon. On cooling, the mixture was triturated with ethanol and water. A gummy solid was collected, dissolved in hot ethyl acetate, filtered and the filtrate was evaporated to give 8.4 g. of crude product (38% yield). Two recrystallizations of this solid from dimethylformamide-acetic acid-water give pure 8-cyano-2-isopropoxy-11-oxo-11H-pyrido[2,1-b]quinazoline, mp 234°-236°.
Reaction SMILES: [N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[C:21]3[N:20]=[C:18](N)[NH:17][C:15](=O)[C:14]=3[N:13]=[CH:12]2)[C@@H:5]1[OH:22])=[N+:2]=[N-:3].[Cl-].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[OH-].[NH4+:34]>N1C=CC=CC=1.O>[N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[C:21]3[N:20]=[CH:18][N:17]=[C:15]([NH2:34])[C:14]=3[N:13]=[CH:12]2)[C@@H:5]1[OH:22])=[N+:2]=[N-:3].[N:1]([C@@H:4]1[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[C:21]3[N:20]=[CH:18][N:17]=[C:15]([NH:34][C:24](=[O:31])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:14]=3[N:13]=[CH:12]2)[C@@H:5]1[OH:22])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=N[C@H]1[C@@H](O)[C@H](n2cnc3c(=O)[nH]c(N)nc32)O[C@@H]1CO
Reactant: O=C(Cl)c1ccccc1
Reactant: [NH4+]
Agent: [Cl-]
Agent: [OH-]
Solvent: c1ccncc1
Solvent: O
Product: [N-]=[N+]=N[C@H]1[C@@H](O)[C@H](n2cnc3c(N)ncnc32)O[C@@H]1CO
Product: [N-]=[N+]=N[C@H]1[C@@H](O)[C@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)O[C@@H]1CO

Procedure:
3′-Azido-3′-deoxyadenosine is synthesized as described by Robins et al. (J. Org. Chem. 66:8204-8210, 2001). 3′-azido-3′-deoxyguanosine (2.92 g; 10 mmol) is dissolved in anhydrous pyridine (60 mL) with vigorous stirring under an argon atmosphere and cooled on an ice bath, followed by treatment with trimethylsylil chloride (3 molar equivalents; mol eq), and stirring for 60 minutes at room temperature. The resulting solution containing the sylilated nucleoside is cooled on an ice bath and treated with benzoyl chloride (1.2 mol eq), allowed to reach room temperature, and then stirred for 4 hours. Water (10 mL) is added and the solution is stirred for 10 minutes. Concentrated ammonium hydroxide (20 mL) is added and the reaction mixture is stirred for 15 minutes at room temperature. The resulting mixture was then evaporated to dryness under reduced pressure. The dried residue is stirred with cold water, filtered, and dried under high vacuum with phosphorus pentoxide, yielding 3′-azido-6-N-benzoyl 3′-deoxyadenosine.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([CH:36]5[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]5)=[CH:32][N:31]=4)[C:26](=[O:42])[N:25]([CH3:43])[N:24]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:58][C:59]([F:62])([F:61])[F:60])(=O)=O.CCOC(C)=O>CN(C=O)C.O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:31]=[CH:32][C:33]([CH:36]5[CH2:41][CH2:40][N:39]([CH2:58][C:59]([F:62])([F:61])[F:60])[CH2:38][CH2:37]5)=[CH:34][CH:35]=4)[C:26](=[O:42])[N:25]([CH3:43])[N:24]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: Cn1nc(-c2cccc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c2CO)cc(Nc2ccc(C3CCNCC3)cn2)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: Cn1nc(-c2cccc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c2CO)cc(Nc2ccc(C3CCN(CC(F)(F)F)CC3)cn2)c1=O
Reaction time: 8 h
Yield: 70.5 %

Procedure:
To a solution of 6-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one (10 mg, 16.4 μmol) in DMF (1 ml) was added potassium carbonate (6.8 mg, 49.2 μmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (3.81 mg, 2.36 μl, 16.4 μmol) at room temperature. The mixture was stirred for 8 h. at the same temperature. EtOAc was added into the reaction mixture (10 mL) and the mixture was poured into water (10 mL). Organic layer was separated, washed with water (4×5 mL), dried (Na2SO4), and evaporated under vacuum. Crude product was purified by preparative tlc (CH2Cl2:MeOH:NH4OH, 90:9.5:0.5) to give 8 mg of pure product (70% yield): m/z 692[M+H]+.
Reaction SMILES: CS(O[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.[H-].[Na+].S([O-])(=O)(=O)C>CN(C=O)C>[N:19]1([CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH:23]=[N:22][CH:21]=[N:20]1
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Reactant: c1nc[nH]n1
Agent: CS(=O)(=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(n2cncn2)CC1
Temperature: 60 °C
Reaction time: 120 h

Procedure:
To a stirred solution of: tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (5.9 g, 21 mmol) and 1,2,4-triazole (1.8 g, 25 mmol equiv.) in DMF at ambient temperature was added sodium hydride (60% in mineral oil, 1.0 g, 25 mmol). The mixture was stirred at 60° C. for 5 days, and the TLC showed no starting mesylate left. The mixture was poured into ice water and extracted with ethyl acetate (3×). The organic layer was dried, evaporated and purified by silica flash column eluting with 0-10% methanol in ethyl acetate to give tert-butyl 4-(1H-1,2,4-triazol-1-yl)piperidine-1-carboxylate as a white solid. The solid was then treated with hydrogen chloride in dioxane (4 N, 10 mL) for 2 h. The mixture was then evaporated to remove most of the dioxane to give a white solid, which was washed with ethyl acetate to give the desired 4-(1H-1,2,4-triazol-1-yl)piperidine hydrochloride salt (5.55 g). 1H NMR (300 MHz, CD3OD): δ 10.00 (s, 1H), 8.97 (s, 1H), 5.10-5.00 (m, 1H), 3.63-3.58 (br. d, 2H), 3.33-3.26 (br. d, 2H), 2.50-2.30 (m, 4H).