Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([N:27]2[C:32]3=[N:33][C:34](S(C)(=O)=O)=[N:35][CH:36]=[C:31]3[CH2:30][N:29]([C:41]3[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:42]=3[Cl:48])[C:28]2=[O:49])[CH:24]=[CH:25][CH:26]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:50]([N:52]([CH2:63][CH3:64])[CH2:53][CH2:54][O:55][C:56]1[CH:62]=[CH:61][C:59]([NH2:60])=[CH:58][CH:57]=1)[CH3:51]>>[Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([N:27]2[C:32]3=[N:33][C:34]([NH:60][C:59]4[CH:58]=[CH:57][C:56]([O:55][CH2:54][CH2:53][N:52]([CH2:63][CH3:64])[CH2:50][CH3:51])=[CH:62][CH:61]=4)=[N:35][CH:36]=[C:31]3[CH2:30][N:29]([C:41]3[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][C:42]=3[Cl:48])[C:28]2=[O:49])[CH:24]=[CH:25][CH:26]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(CC)CCOc1ccc(N)cc1
Reactant: CC(C)(C)[Si](OCCc1cccc(N2C(=O)N(c3ccc(Cl)cc3Cl)Cc3cnc(S(C)(=O)=O)nc32)c1)(c1ccccc1)c1ccccc1
Product: CCN(CC)CCOc1ccc(Nc2ncc3c(n2)N(c2cccc(CCO[Si](c4ccccc4)(c4ccccc4)C(C)(C)C)c2)C(=O)N(c2ccc(Cl)cc2Cl)C3)cc1
Temperature: 180 °C
Yield: 33.2 %

Procedure:
A mixture of 500 mg (0.7 mmol) of 1-[3-(tert-butyldiphenylsilyloxyethyl)phenyl]-3-(2,4-dichlorophenyl)-3,4-dihydro-7-methanesulfonyl-pyrimido[4,5-d]pyrimidin-2(1H)-one and 1 g (4.8 mmol) of 4-[2-(diethylamino)ethoxy]aniline was heated at 180° C. for 30 minutes. The mixture was cooled and the product purified by column chromatography on silica gel using dichloromethane/methanol/acetic acid/water (240:24:3:2) for the elution. Product-containing fractions were combined, evaporated and the residue evaporated with toluene. The residue was then dissolved in 40 ml of dichloromethane, washed with 40 ml of saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and evaporated to afford 200 mg (33%) of 1-[3-(tert-butyldiphenylsilyloxyethyl)phenyl]-3-(2,4-dichlorophenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one as a yellow gum. [Mass spectrum (ESI) MH+ =859].
Reaction SMILES: [Li]CCCC.[CH3:6][C:7](=[N:9][OH:10])[CH3:8].CCCC.C[O:16][C:17](=O)[C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH3:23].Cl>CCCCCC.C1COCC1>[CH3:23][N:19]1[CH2:20][CH2:21][CH2:22][C@H:18]1[C:17](=[O:16])[CH2:6][C:7](=[N:9][OH:10])[CH3:8]
Reactant: CC(C)=NO
Reactant: COC(=O)[C@@H]1CCCN1C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(CC(=O)[C@@H]1CCCN1C)=NO
Temperature: 0 °C
Reaction time: 20 h

Procedure:
To n-BuLi (Aldrich, 2.5M in hexane, 61 4 mL, 1.53 mol, 4.4 eq.), diluted to 1.6M with hexane (342 mL), under argon at 0° C. was added a solution of acetone oxime (Aldrich, 56.15 g, 768 mmol, 2.2 eq.; recrystallized 1x hexanes) in THF (500 mL) dropwise over a 90 minute period (butane evolved!). After an additional 2 hours at 0° C. a solution of N-methyl proline methyl ester (50.0 g, 349 mmoL, 1.0 eq., the product of step 1b above) in THF (75 mL) was added over a 90 minute period. After stirring an additional 20 hours at 0° C. the reaction mixture was slowly cannulated into a vigorously stirred solution of 10% aq. HCl (1700 mL, cooled to 0° C.) over a 40 minute period. The layers were separated and the aqueous layer was washed with ether (1000 mL), then adjusted to pH ~9-10 with NaHCO3 /Na2CO3 (solid) and extracted with methylene chloride (4×800 mL). The combined methylene chloride layers were dried (MgSO4) and concentrated to afford the crude product as a pale yellow oil, (53.62 g), along with 10-20% of the N-oxide byproduct (by NMR integration). MS (Cl, DCl/N H3) m/e 185 (M+H)+. 1NMR (CDCl3) δ: 1.57-1.91 (br.m., 4H); 2.02 (s, 3H); 2.42-2.52 (m, 1H); 2.53 (s, 3H); 2.75 (dd, 1H); 2.80 (d, 2H); 3.15 (m, 1H).
Reaction SMILES: C(O[CH:6]([OH:14])[C:7]([O:9][CH2:10][CH2:11][CH2:12][CH3:13])=[O:8])CCC.[C:15]([NH2:20])(=[O:19])[C:16]([CH3:18])=[CH2:17].COC.C1(C=CC(O)=CC=1)O.C(OC(NC(=O)C=CC)C(OCCCC)=O)CCC>>[C:15]([NH:20][CH:6]([OH:14])[C:7]([O:9][CH2:10][CH2:11][CH2:12][CH3:13])=[O:8])(=[O:19])[C:16]([CH3:18])=[CH2:17]
Reactant: CCCCOC(=O)C(O)OCCCC
Reactant: C=C(C)C(N)=O
Agent: CC=CC(=O)NC(OCCCC)C(=O)OCCCC
Agent: COC
Agent: Oc1ccc(O)cc1
Product: C=C(C)C(=O)NC(O)C(=O)OCCCC
Reaction time: 1.5 h

Procedure:
The procedure of example VI was again followed using the following change: butyl glyoxylate butyl hemiacetal 273 parts; methacrylamide 110 parts; methyl ether of hydroquinone 0.27 parts. The reaction was run at 70° to 75° C. for 1.5 hours. The material was not isolated, instead it was used directly to make butyl methylacrylamidoglycolate butyl ether.
Reaction SMILES: C([Mg]Br)(C)C.C([Li])CCC.[CH2:11]([O:18][C:19]1[CH:24]=[C:23]([F:25])[C:22](Br)=[CH:21][C:20]=1[F:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][O:38][C@H:37]([C:41](=[O:46])N(OC)C)[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>O1CCCC1.O>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][O:38][C@H:37]([C:41](=[O:46])[C:22]2[CH:21]=[C:20]([F:27])[C:19]([O:18][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:24][C:23]=2[F:25])[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]
Reactant: CON(C)C(=O)[C@@H]1CN(C(=O)OC(C)(C)C)CCO1
Reactant: Fc1cc(OCc2ccccc2)c(F)cc1Br
Agent: CC(C)[Mg]Br
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCO[C@H](C(=O)c2cc(F)c(OCc3ccccc3)cc2F)C1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 64.1 %

Procedure:
To a solution of 33 mL of isopropylmagnesium bromide (1M in tetrahydrofuran) in tetrahydrofuran (120 mL) was added with cooling (max+3° C.) n-butyllithium (41 mL, 1.6M in hexane). The mixture was cooled to −78° C., 1-benzyloxy-4-bromo-2,5-difluoro-benzene (8.2 g, 27 mmol) was added and stirred for 1.5 hours at this temperature. (S)-2-(Methoxy-methyl-carbamoyl)-morpholine-4-carboxylic acid tert-butyl ester (7.5 g, 27 mmol) was added dropwise within 10 min at −75° C. Stirring at −78° C. continued for 1 h and the reaction mixture was than poured into water (600 mL). Organic material was partitioned into ethyl acetate (3×), organic phases were pooled, washed with brine and dried with MgSO4 before being concentrated in vacuo. The residue was then purified by column chromatography (heptane-ethyl acetate (2:1)/silica gel) to give 7.5 g of the title compound.
Reaction SMILES: [N:1]([C@@:4]1([OH:19])[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:18]=[CH:17][C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+:2]=[N-:3].C(OC(=O)C)(=O)C.[Br:27]Br>C(O)(=O)C>[N:1]([C@@:4]1([OH:19])[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:18]=[C:17]([Br:27])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=N[C@]1(O)C[C@H](n2ccc(=O)[nH]c2=O)O[C@@H]1CO
Reactant: BrBr
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: [N-]=[N+]=N[C@]1(O)C[C@H](n2cc(Br)c(=O)[nH]c2=O)O[C@@H]1CO
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3'-Azido-5-bromo-2'-doxyuridine was prepared from the known 3'-azido-2'-deoxyuridine (T. A. Krenitsky, et al., J. Med. Chem., 26, 891, (1983)) (0.827 g, 3.3 mMol) by first acetylating the 5'-hydroxyl with acetic anhydride (15 mL) then by brominating the 5 position by the addition of acetic acid (0.5 mL) and bromine (0.566 g). The red-brown solution was stirred at room temperature for two hours. The reaction was taken to an oil in vacuo and triturated with ethyl ether. The oil was dissolved in methanol ammonia to remove the acetyl group. The desired product was isolated by chromatography on silica gel by elution with CHCl3 :MeOH (95:5 v/v). The yield as 32%.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:27]=[C:26]5[C:21]([CH:22]=[CH:23][CH:24]=[N:25]5)=[CH:20][CH:19]=4)=[CH:14][C:13]=3[F:28])[C:8](=[O:11])[NH:9][N:10]=2)[CH2:2]1.[CH3:29][C:30]1([C:33](O)=[O:34])[CH2:32][CH2:31]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.N1(O)C2C=CC=CC=2N=N1>CN(C)C=O>[F:28][C:13]1[CH:14]=[C:15]([C:18]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[CH:20][CH:19]=2)[CH:16]=[CH:17][C:12]=1[N:7]1[C:6]([CH2:5][CH:3]2[CH2:4][N:1]([C:33]([C:30]3([CH3:29])[CH2:32][CH2:31]3)=[O:34])[CH2:2]2)=[N:10][NH:9][C:8]1=[O:11]
Reactant: CC1(C(=O)O)CC1
Reactant: O=c1[nH]nc(CC2CNC2)n1-c1ccc(-c2ccc3cccnc3c2)cc1F
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC1(C(=O)N2CC(Cc3n[nH]c(=O)n3-c3ccc(-c4ccc5cccnc5c4)cc3F)C2)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 9.2 %

Procedure:
In a round bottom flask under nitrogen, a solution of 5-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (1.07 mmol) in N,N-dimethylformamide (5 mL) was treated with 1-methylcyclopropanecarboxylic acid (1.285 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (2.14 mmol), N,N-diisopropylethylamine (3.21 mmol) and then 1H-1,2,3-benzotriazol-1-ol (2.14 mmol). The reaction mixture was stirred at room temperature for 1.5 h and then concentrated in vacuo. Purification of the residue by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH) and subsequent silica gel chromatography (0-3% methanol/ethyl acetate) followed by trituration in ethanol provided the title compound as a white solid (45 mg, 9.2%). MS(ES)+ m/e 458.2 [M+H]+.