Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)(O)[O-].[Na+].[N:6]1[CH:11]=[CH:10][C:9]([SH:12])=[N:8][C:7]=1[SH:13].Cl.[CH2:15]([S:23]SC(=N)N)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>O.CO>[CH2:15]([S:23][S:13][C:7]1[N:8]=[C:9]([S:12][S:23][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH:10]=[CH:11][N:6]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: Sc1ccnc(S)n1
Reactant: CCCCCCCCSSC(=N)N
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCCCCCSSc1ccnc(SSCCCCCCCC)n1
Temperature: 25 °C
Yield: 85 %

Procedure:
A solution of sodium bicarbonate (4.30 g; 0.05 mole) in water (60 ml) was added dropwise to a stirred suspension of pyrimidine-2,4-dithiol prepared as above (2.16 g, 0.015 mole) and S-n-octylthioisothiourea hydrochloride obtained in step (A) (7.695 g, 0.03 mole) in methanol (70 ml) at 60°-65° C. over 30 minutes. The mixture was stirred at room temperature for a further hour and then extracted into naphtha (3×50 ml). The organic extracts were washed with water, dried using anhydrous MgSO4 and evaporated yielding the product as an orange oil (5.54 g; 85%).
Reaction SMILES: [OH:1][C@@H:2]([CH2:34]O)[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:33])[CH:11]([N:17]2[CH2:21][C:20]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[C:24]=3[Cl:31])=[CH:19][C:18]2=[O:32])[CH2:12][C:13]([F:16])([CH3:15])[CH3:14])=[N:5]1.[CH3:36]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.O[C@@H](CO)CN1C=CC(NC(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=N1>ClCCl>[OH:1][C:2]([CH3:34])([CH3:36])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:33])[CH:11]([N:17]2[CH2:21][C:20]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[C:24]=3[Cl:31])=[CH:19][C:18]2=[O:32])[CH2:12][C:13]([F:16])([CH3:14])[CH3:15])=[N:5]1
Reactant: COc1cccc(OC2=CC(=O)N(C(CC(C)(C)F)C(=O)Nc3ccn(C[C@@H](O)CO)n3)C2)c1Cl
Reactant: CCN=C=NCCCN(C)C
Agent: CC(C)C[C@@H](C(=O)Nc1ccn(C[C@@H](O)CO)n1)N1CC(Oc2cccc(Cl)c2Cl)=CC1=O
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COc1cccc(OC2=CC(=O)N(C(CC(C)(C)F)C(=O)Nc3ccn(CC(C)(C)O)n3)C2)c1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 56.8 %

Procedure:
A solution of 2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-fluoro-4-methyl-pentanoic acid (prepared as in Example 170, 200 mg, 0.54 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (92 mg, 0.59 mmol), 1-hydroxybenzotriazole (76 mg, 0.57 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 100 mg, 0.65 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen and then diluted with dichloromethane, washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane) to afford 2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-fluoro-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (156 mg, 57%) as a white powder: LR-ES-MS m/z calculated for C24H30ClFN4O5 [M]+ 508, observed 509 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.05 (br. s., 3H), 1.06 (br. s., 3H), 1.19, 1.32 (2×d, J=3.0 Hz, 3H), 1.26, 1.39 (2×d, J=3.0 Hz, 3H), 1.96-2.33 (m, 2H), 3.90 (br. s., 5H), 4.25 (d, J=18.4 Hz, 1H), 4.52 (d, J=18.4 Hz, 1H), 4.67 (s, 1H), 4.77, 4.80 (2×s, 1H), 5.01, 5.10 (2×dd, J=9.8, 4.4 Hz, 1H), 6.44 (d, J=1.8 Hz, 1H), 7.00, 7.06 (2×d, J=8.2 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 7.54 (d, J=1.8 Hz, 1H), 10.71, 10.82 (2×s, 1H).
Reaction SMILES: [CH:1]([C:3]1[C:11]2[CH:10]=[CH:9][S:8][C:7]=2[C:6]([O:12][C:13]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][N:14]=2)=[CH:5][CH:4]=1)=[O:2].C([O-])([O-])=[O:22].[K+].[K+].OO.O>CS(C)=O>[CH:1]([C:3]1[C:11]2[CH:10]=[CH:9][S:8][C:7]=2[C:6]([O:12][C:13]2[CH:20]=[CH:19][C:16]([C:17]([NH2:18])=[O:22])=[CH:15][N:14]=2)=[CH:5][CH:4]=1)=[O:2]
Reactant: N#Cc1ccc(Oc2ccc(C=O)c3ccsc23)nc1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: NC(=O)c1ccc(Oc2ccc(C=O)c3ccsc23)nc1

Procedure:
6-(4-Formylbenzo[b]thiophen-7-yloxy)nicotinonitrile (Preparation 70) (111 mg, 0.42 mmol) was added to K2CO3 (29 mg, 0.21 mmol) in DMSO (3 mL) followed by H2O2 solution (0.42 mL, 0.42 mmol). After 3 h water was added and the resulting solid filtered and air-dried to give the title compound: RT=2.93 min; m/z (ES+)=283.3 [M+H]+.