Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH:11]2[O:23][CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)=[CH:6][CH:5]=1.[S:35]1[CH:39]=[CH:38][C:37]([CH2:40][C:41](O)=[O:42])=[CH:36]1>>[CH:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:33]=[CH:34][C:25]=1[CH2:24][O:23][CH:11]1[CH:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][O:1][C:41](=[O:42])[CH2:40][C:37]3[CH:38]=[CH:39][S:35][CH:36]=3)=[CH:5][CH:6]=2)[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:12]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(CCO)cc2)C(OCc2ccc3ccccc3c2)C1
Reactant: O=C(O)Cc1ccsc1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(CCOC(=O)Cc3ccsc3)cc2)C(OCc2ccc3ccccc3c2)C1

Procedure:
In an analogous manner to that described in Example 24(g), by condensing tert-butyl (3RS,4RS)-4-[4-(2-hydroxy-ethyl)-phenyl)-3-naphthalen-2-ylmethoxy-piperidine-1-carboxylate and 3-thiopheneacetic acid using 1,1-carbonyldiimidazole as the condensation agent there was obtained tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-[4-(2-thiophen-3-ylacetoxy-ethyl)-phenyl]-piperidine-1-carboxylate as a colourless solid, MS: 603 (M+NH4)+.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([F:26])([F:25])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([OH:24])([CH3:23])[CH3:22])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=O.[NH3:27].CO>C1COCC1>[F:25][C:8]1([F:26])[C:7]2[S:6][C:5]([C:3]([NH2:27])=[O:2])=[N:14][C:13]=2[C:12]2[CH:15]=[C:16]([C:19]#[C:20][C:21]([OH:24])([CH3:23])[CH3:22])[CH:17]=[CH:18][C:11]=2[O:10][CH2:9]1
Reactant: COC(=O)c1nc2c(s1)C(F)(F)COc1ccc(C#CC(C)(C)O)cc1-2
Reactant: N
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(O)C#Cc1ccc2c(c1)-c1nc(C(N)=O)sc1C(F)(F)CO2
Temperature: 25 °C
Reaction time: 3 h
Yield: 30 %

Procedure:
To a solution of 4,4-Difluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (86 mg, 0.227 mmol) in THF (5 mL) at room temperature, NH3/CH3OH (self-made, 5 mL) was added. The mixture was stirred at room temperature for 3 h, then concentrated to give a residue which was purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%) to give 4,4-Difluoro-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as an off-white solid (25 mg, 30%). 1H NMR (400 MHz, DMSO-d6): δ 8.76 (s, 1H), 8.60 (d, J=2.1 Hz, 1H), 8.18 (s, 1H), 7.46 (dd, J1=8.4 Hz, J2=2.2 Hz, 1H), 7.22 (d, J=8.4 Hz, 1H), 5.49 (s, 1H), 4.75 (t, J=10.7 Hz, 2H), 1.49 (s, 6H); LC-MS (ESI & APCI): 365.4 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)=[C:9]([C:28]2[N:32]([CH3:33])[N:31]=[N:30][N:29]=2)[CH:10]=[CH:11][C:12](=[O:27])[CH2:13][CH:14]([OH:26])[CH2:15][C:16]([O:18]CC2C=CC=CC=2)=[O:17])=[CH:4][CH:3]=1.[OH-].[Na+:42]>O1CCCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)=[C:9]([C:28]2[N:32]([CH3:33])[N:31]=[N:30][N:29]=2)[CH:10]=[CH:11][C:12](=[O:27])[CH2:13][CH:14]([OH:26])[CH2:15][C:16]([O-:18])=[O:17])=[CH:6][CH:7]=1.[Na+:42]
Reactant: Cn1nnnc1C(C=CC(=O)CC(O)CC(=O)OCc1ccccc1)=C(c1ccc(F)cc1)c1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cn1nnnc1C(C=CC(=O)CC(O)CC(=O)[O-])=C(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 24 °C
Reaction time: 6 h
Yield: 57.6 %

Procedure:
Phenylmethyl 9,9-bis(4-fluorophenyl)-3-hydroxy-8-(1-methyl-1H-tetrazol-5-yl)-5-oxo-6,8-nonadienoate (0.34g, 0.62 mmole) was dissolved in tetrahydrofuran (4mL) and water (1mL). 1N Sodium hydroxide (0.62 mL, 0.62 mmole) was added, and the solution was stirred for 6 hours at 24° C. The mixture was diluted with water (10 mL) and washed with diethyl ether (3×50 mL). The aqueous portion was lyophilized to give 0.17 g (52%) of the title compound; m.p.=166°-180° C. (dec.).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[NH:14][CH:13]=[C:12]([CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:11]=2[F:25])=[CH:8][CH:7]=[CH:6][N:5]=1.C1OCCOCCOCCOCCOC1.[S:41]1[CH:45]=[CH:44][C:43]([S:46](Cl)(=[O:48])=[O:47])=[CH:42]1>O1CCCC1.O>[F:25][C:11]1[C:12]([CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[CH:13][N:14]([S:46]([C:43]2[CH:44]=[CH:45][S:41][CH:42]=2)(=[O:48])=[O:47])[C:10]=1[C:9]1[C:4]([F:3])=[N:5][CH:6]=[CH:7][CH:8]=1
Reactant: CN(Cc1c[nH]c(-c2cccnc2F)c1F)C(=O)OC(C)(C)C
Reactant: O=S(=O)(Cl)c1ccsc1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CN(Cc1cn(S(=O)(=O)c2ccsc2)c(-c2cccnc2F)c1F)C(=O)OC(C)(C)C
Reaction time: 2 h
Yield: 91 %

Procedure:
To a suspension of sodium hydride (60% in oil, 37 mg) in tetrahydrofuran (2 mL) were added a solution of tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate in tetrahydrofuran (1 mL), 15-crown-5 (205 mg) and 3-thiophenesulfonyl chloride (136 mg) at room temperature and the mixture was stirred for 2 hr. The reaction mixture was diluted with water, and extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=6:1→3:2) to give the title compound as a pale-yellow oil (yield 264 mg, 91%).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[CH:21]=[CH:22][C:23]4[O:27][C:26]([C:28](OC)=[O:29])=[CH:25][C:24]=4[CH:32]=3)[N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:34][NH2:35]>>[C:1]([C:5]1[CH:6]=[C:7]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[CH:21]=[CH:22][C:23]4[O:27][C:26]([C:28]([NH:35][CH3:34])=[O:29])=[CH:25][C:24]=4[CH:32]=3)[N:13]=2)[CH:8]=[CH:9][CH:10]=1)([CH3:2])([CH3:4])[CH3:3]
Reactant: COC(=O)c1cc2cc(Nc3ncc(F)c(Nc4cccc(C(C)(C)C)c4)n3)ccc2o1
Reactant: CN
Agent: Cl
Product: CNC(=O)c1cc2cc(Nc3ncc(F)c(Nc4cccc(C(C)(C)C)c4)n3)ccc2o1

Procedure:
In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-[3-(N-methylamino)carbonylmethyleneoxyphenyl]-2,4-pyrimidinediamine, N4-(3-tert-butylphenyl)-5-fluoro-N2-(2-methoxycarbonylbenzofur-5-yl)-2,4-pyrimidinediamine and methylamine hydrochloride were reacted to give N4-(3-tert-butylphenyl)-5-fluoro-N2-[2-(N-methylamino)carbonylbenzofur-5-yl]-2,4-pyrimidinediamine. LCMS: ret. time: 23.05 min.; purity: 100%; MS (m/e): 434 (MH+); 1□ □ □ □ □ (DMSO-d6): δ 9.6 (1H, s), 9.57 (1H, s), 8.75 (1H, m), 8.25 (1H, s), 8.15 (1H, s), 7.93 (1H, d, J=8.5 Hz), 7.47 (3H, m), 7.44 (1H, s), 7.36 (1H, t, J=8.5 Hz), 7.25 (1H, d, J=8.5 Hz), 2.89 (3H, d, J=4.5 Hz), 1.33 (9H, s).
Reaction SMILES: [N:1]1([C@@H:6]2[CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:26]=[CH:25][C:24]5[C:19](=[CH:20][CH:21]=[C:22]([OH:27])[CH:23]=5)[C:18]4=[O:28])=[CH:13][C:12]=3[F:29])[CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+].[CH:32]12[O:38][CH:37]1[CH2:36][CH2:35][O:34][CH2:33]2>>[N:1]1([C@@H:6]2[CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH:26]=[CH:25][C:24]5[C:19](=[CH:20][CH:21]=[C:22]([O:27][C@H:32]6[C@H:37]([OH:38])[CH2:36][CH2:35][O:34][CH2:33]6)[CH:23]=5)[C:18]4=[O:28])=[CH:13][C:12]=3[F:29])[CH2:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=c1c2ccc(O)cc2ccn1-c1ccc(N2CC[C@@H](N3CCCC3)C2)c(F)c1
Reactant: C1CC2OC2CO1
Agent: [Cs+]
Agent: [F-]
Product: O=c1c2ccc(O[C@@H]3COCC[C@H]3O)cc2ccn1-c1ccc(N2CC[C@@H](N3CCCC3)C2)c(F)c1

Procedure:
According to Method T, 2-((R)-4-[1,3′]bipyrrolidinyl-1′-yl-3-fluorophenyl)-6-hydroxy-2H-isoquinolin-1-one, with cesium fluoride as auxiliary base, was reacted with 3,7-dioxa-bicyclo[4.1.0]heptane. In this way the product was obtained with molecular weight 493.58 (C28H32FN3O4); MS (ESI): 494 (M+H+).