Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[C-:10]#[N:11].[Na+]>CN1CCCC1=O>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:10]#[N:11])=[CH:3][C:4]=1[F:9]
Reactant: Nc1ccc(Br)cc1F
Reactant: [C-]#N
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: N#Cc1ccc(N)c(F)c1

Procedure:
6.8 Parts of 4-bromo-2-fluoroaniline were dissolved in 75 parts of N-methylpyrrolidone. This solution was treated with 4.2 parts of cuprous cyanide. The reaction mixture was heated to 190° for 2 hours. The reaction mass was poured onto a mixture of 200 parts of ice and 15 parts of sodium cyanide. This mixture was then heated on a steam bath for 2 hours at 60°-70°. This aqueous solution was then extracted with four 100 ml portions of toluene. The toluene extracts were combined and washed with four 300-ml portions of water followed by 100 ml of saturated NaCl. The toluene solution of the product was dried over sodium sulfate and stripped to give 2.6 parts of the desired product, m.p. 71°-73°.
Reaction SMILES: N[C:2](N)=[S:3].[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[F:14])CBr.Cl>C(O)C.[OH-].[Na+]>[F:5][C:6]1[CH:7]=[C:8]([CH2:2][SH:3])[CH:11]=[CH:12][C:13]=1[F:14]
Reactant: Fc1ccc(CBr)cc1F
Reactant: NC(N)=S
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Fc1ccc(CS)cc1F
Temperature: 25 °C

Procedure:
Thiourea (5.0 g) was added to a solution of 3,4-difluorobenzyl bromide (13.6 g) in ethanol (100 ml). The mixture was heated at reflux for 3 h before removal of the volatiles in vacuo. The crude solid was suspended in aqueous sodium hydroxide solution (1.6M, 110 ml) and heated at reflux for 3 h before allowing to cool to room temperature. The reaction was acidified with concentrated hydrochloric acid and the organics extracted with ether (200 ml). The organic layer was washed with saturated sodium bicarbonate solution (2×50 ml), brine (20 ml), dried (MgSO4), and concentrated in vacuo to provide the subtitle product as a colourless oil. Yield 11.1 g
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[N:7]([CH2:15][C:16]([OH:18])=O)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:19]#[N:20].[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]([NH:29][NH2:30])=O>>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([C:11]([F:12])([F:13])[F:14])[N:7]([CH2:15][C:16]3[O:18][C:27]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=4)=[N:29][N:30]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:19]#[N:20]
Reactant: N#Cc1ccc2c(nc(C(F)(F)F)n2CC(=O)O)c1Cl
Reactant: NNC(=O)c1ccccn1
Product: N#Cc1ccc2c(nc(C(F)(F)F)n2Cc2nnc(-c3ccccn3)o2)c1Cl

Procedure:
Synthesized as described Example 200C from [4-chloro-5-cyano-2-(trifluoromethyl)-1H-benzimidazol-1-yl]acetic acid and 2-pyridinecarbohydrazide: MS (ESI) m/z 405 (M+1).
Reaction SMILES: [O:1]([CH2:9][CH2:10][C:11]#[CH:12])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C([Li])CCC.[CH3:18][Si:19](Cl)([CH3:21])[CH3:20]>C1COCC1.CCCCCC>[CH3:18][Si:19]([CH3:21])([CH3:20])[C:12]#[C:11][CH2:10][CH2:9][O:1][Si:2]([C:5]([CH3:6])([CH3:7])[CH3:8])([CH3:3])[CH3:4]
Reactant: C[Si](C)(C)Cl
Reactant: C#CCCO[Si](C)(C)C(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)(C)[Si](C)(C)OCCC#C[Si](C)(C)C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 86.6 %

Procedure:
To a solution of 1-(t-butyldimethylsiloxy)-3-butyne (49.0 g, 0.27 mol) in 250 mL of THF, at -78° C. under Ar, was added a solution of n-butyllithium (1.6 M in hexane, 170 mL, 0.27 mol) over ca. 45 min. The mixture was stirred at -78° C. for 30 min and then at 0° C. for 1.5 h. The resulting solution was recooled at -78° C. and then trimethylsilyl chloride (34.0 mL, 0.27 mol) was added dropwise. After the addition the mixture was allowed to warm to room temperature over 18 h and then it was diluted with hexane, washed (H2O, sat. aq. NaHCO3, brine), dried (Na2SO4) and evaporated to give an oil. Distillation at reduced pressure afforded the title compound (60.0 g, 88%) as a colourless oil, bp 70°-75° C./0.1 mm: IR (neat) 2180, 1253, 1112, 841 cm-1 ; 1H NMR (CDCl3, 200 MHz) δ3.72 (t, J=7.0 Hz, 2H), 2.43 (t, J=7.0 Hz, 2H), 0.90 (s, 9H), 0.14 (s, 9H), 0.07 (s, 6H).
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].Br[CH2:14][CH:15]=[CH:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][CH:18]=1.C(N(CC)CC)C>CN1CCCC1=O>[Br:23][C:20]1[CH:21]=[CH:22][C:17]([CH:16]=[CH:15][CH2:14][O:1][N:2]2[C:3](=[O:12])[C:4]3=[CH:11][CH:10]=[CH:9][CH:8]=[C:5]3[C:6]2=[O:7])=[CH:18][CH:19]=1
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: BrCC=Cc1ccc(Br)cc1
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2C(=O)N1OCC=Cc1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 96 h
Yield: 87.1 %

Procedure:
18.5 g (0.11 mol) of N-hydroxyphthalimide and 31.4 g (0.11 mol) of 1-bromo-[3-(4-bromophenyl)]-prop-2-ene were added in succession to 350 ml of dry N-methylpyrrolidone, and 12.1 g (0.12 mol) of triethylamine were then added dropwise at room temperature. After stirring had been carried out for four days at 20° C., the reaction mixture was poured onto 1.5 1 of ice water and the solid was filtered off and washed with water and isopropanol. 34.3 g (86.8% of theory) of N-[3-(4-bromophenyl)-prop-2-enyloxy]-phthalimide with a melting point of 161°-162° C. were obtained.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[N:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1.[NH2:14][C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=1[S:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1>>[CH3:13][C:4]1[CH:3]=[C:2]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[S:22][C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[C:11]2[C:6](=[N:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=1
Reactant: Cc1ccc2c(Cl)cc(C)nc2n1
Reactant: Cc1ccc(Sc2ccc(O)cc2)c(N)c1
Product: Cc1ccc(Sc2ccc(O)cc2)c(Nc2cc(C)nc3nc(C)ccc23)c1

Procedure:
The product from Example 14b (60 mg, 0.31 mmol) was reacted with the product from Example 4c (72 mg, 0.31 mmol) for 12 h following the procedure from Example 1g giving the title compound as a crude solid which was purified by HPLC with TFA giving the product as a trifluoroacetic acid salt (45 mg, 37%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 2.23 (s, 3H) 2.75 (s, 3H) 3.43 (s, 3H) 6.10 (s, 1H) 6.68 (d, J=8.82 Hz, 2H) 6.99-7.20 (m, 3H) 7.20-7.38 (m, 2H) 7.75 (d, J=8.82 Hz, 1H) 8.96 (d, J=8.82 Hz, 1H) 9.86 (s, 1H) 10.78 (s, 1H) 14.21 (s, 1H); MS (APCI) m/z 386 (M−H)−.
Reaction SMILES: CON(C)[C:4]([C@@H:6]1[O:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)=[O:5].[CH3:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][Mg]Cl>C1COCC1>[CH3:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][C:4]([C@@H:6]1[O:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:7]1)=[O:5]
Reactant: COCCCC[Mg]Cl
Reactant: CON(C)C(=O)[C@H]1CN(C(=O)OC(C)(C)C)CCO1
Solvent: C1CCOC1
Product: COCCCCC(=O)[C@H]1CN(C(=O)OC(C)(C)C)CCO1
Temperature: 25 °C
Yield: 93 %

Procedure:
To a solution of (R)-tert-butyl 2-(methoxy(methyl)carbamoyl)morpholine-4-carboxylate (1.37 g, 5.0 mmol) in THF (10 mL) at −20° C., there was added (4-methoxybutyl)magnesium chloride in THF (1.47 M, 10.2 mL, 15.0 mmol) dropwise such that the temperature remained below −20° C. After addition, the resulting solution was warmed to rt, and quenched with 1 N aq HCl (10 mL). The organic layer was separated, and the aqueous layer was extracted with ether (3×5 mL). The combined organic layers were washed with satd aq NaHCO3 (10 mL) and brine (5 mL), and dried over Na2SO4. The solvent was then removed in vacuo to give (R)-tert-butyl 2-(5-methoxypentanoyl)morpholine-4-carboxylate (1.41 g, 93%), which was used for the next step without purification; MS m/s 324 (M+Na+).