Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[N:10]([C:35]([CH2:38][OH:39])=[N:36][N:37]=3)[N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]=2[C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.C(N(CC)[P:43]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])C.N1C=NC=N1.OO.[O-:63]S([O-])=O.[Na+].[Na+]>ClCCCl>[P:43]([O:39][CH2:38][C:35]1[N:10]2[N:11]([CH2:23][C:24]3[C:25]([CH3:34])=[N:26][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:28][CH:29]=3)[C:12](=[O:22])[C:13]([C:14]3[CH:15]=[CH:16][C:17]([C:18]#[N:19])=[CH:20][CH:21]=3)=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:9]2=[N:37][N:36]=1)([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:63]
Reactant: CCN(CC)P(OC(C)(C)C)OC(C)(C)C
Reactant: Cc1nc(C(F)(F)F)ccc1Cn1c(=O)c(-c2ccc(C#N)cc2)c(-c2ccc(Cl)cc2)c2nnc(CO)n21
Reactant: O=S([O-])[O-]
Agent: OO
Agent: [Na+]
Agent: c1nc[nH]n1
Solvent: ClCCCl
Product: Cc1nc(C(F)(F)F)ccc1Cn1c(=O)c(-c2ccc(C#N)cc2)c(-c2ccc(Cl)cc2)c2nnc(COP(=O)(OC(C)(C)C)OC(C)(C)C)n21
Temperature: 60 °C
Reaction time: 24 h

Procedure:
To a round bottom flask was added 4-(8-(4-chlorophenyl)-3-(hydroxymethyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)benzonitrile (25 mg, 0.0454 mmol), di-tert-butyl diethylphosphoramidite (34 mg, 0.136 mmol), 1,2,4-triazole (9.5 mg, 0.136 mmol) and 1,2-dichloroethane (3 ml). The reaction was stirred at 60° C. for 24 hr. After this time the reaction was cooled to rt. H2O2(7 N, 0.5 ml) was then added and the reaction was stirred at rt for 60 min. Na2SO3 (10%, 1 ml) was added and the reaction was stirred at rt for an additional 30 min. After this time, the reaction mixture was concentrated. The residue was diluted with EtOAc (50 ml) and the resulting solution was washed with water (25 ml) and saturated NaCl (25 ml). The organic layer was dried over MgSO4, filtered and concentrated. The crude intermediate was purified by silica gel column chromatography (4 g silica gel) eluting with a gradient of 0-50% EtOAc/Hex to give di-tert-butyl (8-(4-chlorophenyl)-7-(4-cyanophenyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl phosphate as clear oil. To this purified intermediate was added CH2Cl2(2 ml) and TFA (0.5 ml). The reaction was stirred at rt for 10 min. After this time the solution was concentrated. The crude product was purified by preparative HPLC eluting with water/MeOH to give the product (28 mg). The product was then dissolved in water (1 ml) and 1N NaOH (1N, 0.0445 mmol) was added. The resulting solution was concentrated on a lyophilizer to give the title compound, sodium (8-(4-chlorophenyl)-7-(4-cyanophenyl)-5-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl hydrogenphosphate, as a white solid (29 mg, 94%).
Reaction SMILES: [CH2:1]([C:3]1([OH:14])[CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4]1)[CH3:2].[C:15]([OH:21])([C:17]([F:20])([F:19])[F:18])=[O:16]>C(Cl)Cl>[F:18][C:17]([F:20])([F:19])[C:15]([OH:21])=[O:16].[CH2:1]([C:3]1([OH:14])[CH2:6][NH:5][CH2:4]1)[CH3:2]
Reactant: CCC1(O)CN(C(=O)OC(C)(C)C)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCC1(O)CNC1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
tert-Butyl 3-ethyl-3-hydroxyazetidine-1-carboxylate (2.3 g, 11.43 mmol) was dissolved in DCM (10 mL) and TFA (15 mL) was added. The reaction mixture was stirred at RT for 2.5 h and then the mixture was evaporated. Ethanol was added and the mixture was again evaporated to afford 3.0 g (100%) of 70A. 1H NMR (500 MHz, CDCl3): δ 0.96 (t, 3H), 1.81 (q, 2H), 3.94 (m, 4H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][C:20]([O:25][CH3:26])=[N:21][C:22]([O:23]C)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].O1CCOCC1.Cl>O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[N:19]=[C:20]([O:25][CH3:26])[NH:21][C:22](=[O:23])[C:17]=3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1nc(OC)c2cnn(C3CCN(C(=O)OC(C)(C)C)CC3)c2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: COc1nc2c(cnn2C2CCN(C(=O)OC(C)(C)C)CC2)c(=O)[nH]1
Temperature: 40 °C

Procedure:
A mixture of 4-(4,6-dimethoxy-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (1 mmol), 2 M aqueous sodium hydroxide (1 mL) and dioxane (10 mL) is heated at 40° C. for 5 h. The mixture is allowed to cool, and is then neutralized to approximately pH 7 by the addition of 1 M aqueous hydrochloric acid. Ethyl acetate and water are added. The organic layer is washed with water and brine, dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography on silica gel to give 4-(6-methoxy-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [C:1]([O-:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[Na+].COC1C=CC(O)=CC=1.[CH:17]([O:19][CH2:20][CH2:21]Cl)=[CH2:18].[OH-].[Na+]>CS(C)=O.O.C(Cl)(Cl)Cl>[C:1]([O:6][CH2:21][CH2:20][O:19][CH:17]=[CH2:18])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)[O-]
Reactant: C=COCCCl
Agent: COc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: C=COCCOC(=O)C(=C)C
Temperature: 80 °C

Procedure:
40 g of sodium methacrylate was suspended in 300 g of dimethylsulfoxide (DMSO) in a 2 L flask equipped with a mechanical stirrer, cold water condenser and heating mantle. 0.35 g of 4-methoxyphenol was added. The mixture was heated to 80° C. with stirring under a nitrogen blanket. During heating, 36 g of 2-chloroethyl vinyl ether was added over 30 minutes. The reaction was then maintained at 80° C. for 20 hr. After the reaction solution was cooled to room temperature, 0.45 g of sodium hydroxide dissolved in 300 ml of water was added and the mixture was stirred for 20 minutes. About 500 g of chloroform was then added and the resulting mixture was stirred for 30 minutes. The mixture was then transferred into a separatory funnel. The bottom layer was separated and discarded. The chloroform layer was washed thoroughly with deionized (Dl) water and dried with sodium sulfate. The filtrate was then subjected to rotary evaporation at room temperature to remove most of the volatile materials. The lightly colored liquid was consistent with 2-vinyloxyethyl methacrylate (VEMA) by proton NMR: (in CDCl3): 1.98 ppm (3H CH3), 3.8 ppm (2H C(O)CH2CH2-O), 4.3 ppm (2 H C(O)CH2CH2-O), 4.0 ppm and 4.2 ppm (2H OCHCH2), 5.5 ppm and 6.2 ppm (2H CH2=C(CH3)), 6.5 ppm (1H OCHCH2).