Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(C(C)C)C(C)C)C.[Br-].[Li+].Cl[CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1.[CH3:24][N:25]1[C:30](=[O:31])[C:29]2[CH2:32][NH:33][CH2:34][CH2:35][C:28]=2[NH:27][C:26]1=[O:36]>CN(C)C=O>[CH3:24][N:25]1[C:30](=[O:31])[C:29]2[CH2:32][N:33]([CH2:13][CH2:14][CH2:15][CH2:16][O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[CH2:34][CH2:35][C:28]=2[NH:27][C:26]1=[O:36]
Reactant: Cn1c(=O)[nH]c2c(c1=O)CNCC2
Reactant: ClCCCCOC1CCCCO1
Agent: [Br-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1c(=O)[nH]c2c(c1=O)CN(CCCCOC1CCCCO1)CC2
Yield: 51 %

Procedure:
27 g of ethyldiisopropylamine, 18 g of lithium bromide and 46 g of 2-(4-chlorobutoxy) tetrahydropyran (86.3% pure according to GC) were added to 36.3 g of 3-methyl-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione in 1 l of dimethylformamide, with stirring, and the mixture was stirred for 5 h at 70° C. It was concentrated under reduced pressure and 34.5 g of crude 3-methyl-6-[4-(tetrahydropyran-2-yloxy)butyl]-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione were obtained after working-up of the residue by extraction with dichloromethane and water and after drying and concentration of the combined dichloromethane phases, and this crude product was purified by column chromatography on aluminum oxide (actiVity grade III) and elution with dichloromethane/ethanol (volume ratio 90:10).
Reaction SMILES: [OH-].[NH4+:2].[F:3][C:4]1[CH:9]=[C:8]([Br:10])[C:7]([F:11])=[CH:6][C:5]=1[S:12](Cl)(=[O:14])=[O:13].O>O1CCCC1>[Br:10][C:8]1[C:7]([F:11])=[CH:6][C:5]([S:12]([NH2:2])(=[O:14])=[O:13])=[C:4]([F:3])[CH:9]=1
Reactant: [NH4+]
Reactant: O=S(=O)(Cl)c1cc(F)c(Br)cc1F
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: NS(=O)(=O)c1cc(F)c(Br)cc1F
Reaction time: 0.17 h

Procedure:
Ammonium hydroxide (5 ml) was added to a solution of 2,5-difluoro-4-bromophenylsulfonyl chloride (4.3 g) in tetrahydrofuran (20 ml) at room temperature (CARE:exotherm) and stirred for 10 min. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated and the residue triturated with 20% diethyl ether in isohexane to give the sub-title compound as a solid (4.3 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:5]2[N:15]=[C:16]([C:18]3[C:27]([CH3:28])=[N:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH:17]=[C:4]2[N:3]=1.[C:29]1(B(O)O)[CH2:33][CH2:32][CH2:31][CH:30]=1.[F-].[Cs+].O>COCCOC.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:29]1([C:2]2[CH:7]=[C:6]([NH:8][CH:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[N:5]3[N:15]=[C:16]([C:18]4[C:27]([CH3:28])=[N:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[CH:17]=[C:4]3[N:3]=2)[CH2:33][CH2:32][CH2:31][CH:30]=1
Reactant: Cc1nc2ccccc2nc1-c1cc2nc(Cl)cc(NC3CCOCC3)n2n1
Reactant: OB(O)C1=CCCC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Solvent: O
Product: Cc1nc2ccccc2nc1-c1cc2nc(C3=CCCC3)cc(NC3CCOCC3)n2n1
Temperature: 80 °C

Procedure:
A suspension of 5-chloro-2-(3-methylquinoxalin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (Example 1.001 (g)) (97 mg, 0.246 mmol), cyclopenten-1-ylboronic acid (55 mg, 0.491 mmol), tetrakis(triphenylphosphine)palladium(0) (57 mg, 0.0493 mmol), and cesium fluoride (112 mg, 0.737 mmol) in 1,2-dimethoxyethane (2.0 mL) was heated at 80° C. for 3 h. After being cooled to ambient temperature, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, filtrated and concentrated in vacuo. The crude was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 2:3) to give 5-cyclopent-1-en-1-yl-2-(3-methylquinoxalin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (the compound of Example 1.011 listed in the Table of Examples as described hereinafter). 1H-NMR (400 MHz, CDCl3): δ 1.73-1.86 (2H, m), 2.03-2.21 (4H, m), 2.60-2.66 (2H, m), 2.86-2.93 (2H, m), 3.05 (3H, s), 3.61 (2H, ddd, J=11.8, 11.8, 2.4 Hz), 3.77-3.87 (1H, m), 4.10 (2H, ddd, J=11.8, 3.3, 3.3 Hz), 6.19 (1H, s), 6.33 (1H, d, J=8.2 Hz), 6.68 (1H, s), 7.08 (1H, s), 7.72-7.79 (2H, m), 8.04-8.08 (1H, m), 8.17-8.21 (1H, m).
Reaction SMILES: C(Br)Br.[CH3:4]N(C)C=O.[Cl:9][C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][NH:16][C:17](=[S:19])[S-:18])=[CH:12][CH:11]=1.[K+].S1CCS1>O>[Cl:9][C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][N:16]=[C:17]2[S:18][CH2:4][S:19]2)=[CH:12][CH:11]=1
Reactant: S=C([S-])NCOc1ccc(Cl)cc1
Reactant: CN(C)C=O
Agent: C1CSS1
Agent: [K+]
Solvent: O
Solvent: BrCBr
Product: Clc1ccc(OCN=C2SCS2)cc1
Reaction time: 1.5 h

Procedure:
To a mixture of 19.3 g. of methylene bromide and 3.7 g. of treithylamine in 100 ml. of dimethylformamide was added 10.0 g. of potassium p-chlorophenoxymethyldithiocarbamate in portions. After another 1 to 2 hours, the mixture was poured into water and partitioned into ethylene chloride. The dried ethylene chloride mixture was saturated with dry hydrogen chloride and the resulting salt collected by filtration. Hydrolysis of the salt in a chloroform-water mixture followed by separation, drying and concentration of the chloroform layer gave 3.5 g. of the dithietane as pale yellow crystals, m.p. 64.5°-66.0°C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:20]2[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]2=[O:30])[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:12][CH:13]=1.Br[C:32]1[N:33]([CH2:40][C:41]2([CH3:44])[CH2:43][O:42]2)[CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[N:36]=1.C(N(C(C)C)CC)(C)C>C(OC(O)C)C>[F:1][C:2]1[CH:3]=[C:4]([N:20]2[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]2=[O:30])[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([CH2:43][C:41]3([CH3:44])[O:42][C:32]4=[N:36][C:35]([N+:37]([O-:39])=[O:38])=[CH:34][N:33]4[CH2:40]3)[CH2:16][CH2:15]2)=[CH:12][CH:13]=1
Reactant: CC1(Cn2cc([N+](=O)[O-])nc2Br)CO1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(-c3ccc(N4CCNCC4)nc3)c(F)c2)C(=O)O1
Agent: CCOC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)NC[C@H]1CN(c2ccc(-c3ccc(N4CCN(CC5(C)Cn6cc([N+](=O)[O-])nc6O5)CC4)nc3)c(F)c2)C(=O)O1
Yield: 12 %

Procedure:
A solution of N-[((5S)-3-{3-fluoro-4-[6-(1-piperazinyl)-3-pyridinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide (0.147 g, 0.355 mmol), 2-bromo-1-[(2-methyl-2-oxiranyl)methyl]-4-nitro-1H-imidazole (0.092 g, 0.35 mmol) and diisopropylethylamine (70 μL, 0.40 mmol) in ethoxyethanol (10 mL) was refluxed for 2.5 h. The solution was evaporated onto silica gel, column chromatography (0-10% MeOH/EtOAc, gradient elution) gave a solid which was reprecipitated from refluxing MeOH to give the titled compound (25 mg, 12%) as a cream solid. APCI MS m/z 595 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 8.28 (bs, 1H), 8.21 (t, J=5.8 Hz, 1H), 8.12 (s, 1H), 7.70 (bdt, J=9.0, 2.2 Hz, 1H), 7.51-7.59 (m, 2H), 7.37 (dd, J=8.6, 2.2 Hz, 1H), 6.88 (d, J=9.0 Hz, 1H), 4.71-4.79 (m, 1H), 4.29 (d, J=10.7 Hz, 1H), 4.15 (t, J=9.0 Hz, 1H), 4.09 (d, J=10.7 Hz, 1H), 3.77 (dd, J=9.2, 6.5 Hz, 1H), 3.31-3.47 (m, 6H), 2.82 (d, J=14.7 Hz, 1H), 2.78 (d, J=14.7 Hz, 1H), 2.72-2.79 (m, 4H), 1.84 (s, 3H), 1.58 (s, 3H).
Reaction SMILES: [OH:1][CH:2]([C:4]1([CH3:18])[CH2:8][NH:7][CH2:6][CH:5]1[C:9]1[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([OH:15])[CH:14]=1)[CH3:3].CCN(C(C)C)C(C)C.[CH3:28][C:29]1([CH3:37])[O:33][C@H:32]([C:34](Cl)=[O:35])[CH2:31][O:30]1>C(Cl)Cl>[CH3:28][C:29]1([CH3:37])[O:33][C@@H:32]([C:34]([N:7]2[CH2:6][C@@H:5]([C:9]3[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([OH:15])[CH:14]=3)[C@@:4]([C@H:2]([OH:1])[CH3:3])([CH3:18])[CH2:8]2)=[O:35])[CH2:31][O:30]1
Reactant: COc1ccc(C2CNCC2(C)C(C)O)cc1O
Reactant: CC1(C)OC[C@@H](C(=O)Cl)O1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc([C@@H]2CN(C(=O)[C@H]3COC(C)(C)O3)C[C@@]2(C)[C@@H](C)O)cc1O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A round bottom flask equipped with a stir bar and rubber septum was charged with 5-[4-(1-hydroxy-ethyl)-4-methylpyrrolidin-3-yl)-2-methoxyphenol (2.4 g, 9.55 mmol), dry CH2Cl2 (50 mls), and DIEA (3.49 mls, 20.1 mmol) under a nitrogen atmosphere. The mixture was chilled to 0° C. and (S)-2.2-dimethyl-[1,3]dioxolane-4-carbonyl chloride (3.14 g, 19.1 mmol) in 15 ml of CH2Cl2 was added dropwise by syringe. The reaction mixture was allowed to gradually warm to room temperature over a 16-hour period. The mixture then was diluted with 50 ml of CH2Cl2, washed with 1N HCl (2×50 ml), saturated aqueous NaHCO3 (1×50 ml), dried over Na2SO4, and concentrated to 3.9 g of a tan foam. The material was taken up in 100 ml CH3OH and chilled to 0° C. Three equivalents of aqueous 1N LiOH then were added (29 ml, 29.0 mmol), the mixture was stirred at 0° C. for 2 hours, then warmed to room temperature for 2 hours. The reaction mixture next was concentrated under reduced pressure with the bath temperature at 30° C. to remove CH3OH. The remaining aqueous material was neutralized with saturated NH4Cl to pH 7 and extracted with EtOAc (2×100 ml). The extracts were dried over Na2SO4 and concentrated to 2.74 g of a tan foam (76%).
Reaction SMILES: C([Li])CCC.[CH2:6]([O:8][S:9]([CH2:12]P(OCC)(OCC)=O)(=[O:11])=[O:10])[CH3:7].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[C:24]([O:30][CH3:31])[CH:23]=1>C1COCC1>[CH2:6]([O:8][S:9]([CH:12]=[CH:26][C:25]1[CH:28]=[CH:29][C:22]([Cl:21])=[CH:23][C:24]=1[O:30][CH3:31])(=[O:10])=[O:11])[CH3:7]
Reactant: CCOP(=O)(CS(=O)(=O)OCC)OCC
Reactant: COc1cc(Cl)ccc1C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOS(=O)(=O)C=Cc1ccc(Cl)cc1OC
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 99.9 %

Procedure:
A 2.5M solution of n-butyllithium in hexanes (6.15 mL, 15.37 mmol) was added dropwise to a stirred solution of (diethoxy-phosphoryl)-methanesulfonic acid ethyl ester (4.0 g, 15.37 mmol) in THF (200 mL) at −78° C. The reaction mixture was stirred at −78° C. for 15 minutes. A solution of 4-chloro-2-methoxy-benzaldehyde (2.41 g, 14.10 mmol) in THF (20 mL) was then added dropwise. After the addition was complete the reaction mixture was warmed to RT, stirred for 1 h and quenched with brine. The reaction mixture was concentrated under reduced pressure and DCM (200 mL) was added. The organic layer was separated, washed with brine (3×100 mL) and dried over MgSO4. Removal of solvent under reduced pressure, followed by purification on silica gel using hexane/ethyl acetate, 4:1 to 2:1 afforded the title compound (3.90 g, quantitative) as a white solid.
Reaction SMILES: [CH2:1]([N:8]([CH2:19][CH3:20])[C:9](=[O:18])[CH2:10][CH2:11][CH2:12][CH2:13][C:14](OC)=[O:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[BH4-].[Na+].CO>C(O)(C)(C)C>[CH2:1]([N:8]([CH2:19][CH3:20])[C:9](=[O:18])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][OH:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCN(CC)C(=O)CCCCC(=O)OC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CC(C)(C)O
Product: CCCCCCCN(CC)C(=O)CCCCCO
Yield: 35.8 %

Procedure:
A mixture of a solution of 3.1 gms of the N-heptyl-N-ethyladipamic acid, methyl ester in 40 ml of tert-butanol and 800 mg of sodium borohydride is heated to reflux, following which 7.8 ml of methanol is added dropwise. The reaction mixture is stirred at reflux for 18 hours and then partitioned between water and CH2Cl2. After separation, the organic layer is dried over MgSO4, filtered, and concentrated under vacuum. The residue obtained is flash chromatographed on normal phase silica gel with a 4/1 ratio of hexane and ethyl acetate to yield 1.0 gms of N-heptyl-N-ethyl(6-hydroxy)hexanamide.