Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:6]2[CH2:7][CH2:8][NH:9][C:10](=[O:11])[C:5]2=[C:4]([CH3:12])[C:3]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[CH:28]=[CH:27][C:23](C(O)=O)=[CH:22][C:21]=2OC)[N:14]=1.N[CH:32]1C[CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1.CN(C([O:46]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH3:1][C:2]1[N:6]2[CH2:7][CH2:8][NH:9][C:10](=[O:11])[C:5]2=[C:4]([CH3:12])[C:3]=1[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[CH:28]=[C:27]([CH2:32][CH2:33][C:34]([N:35]([CH3:38])[CH3:36])=[O:46])[CH:23]=[CH:22][CH:21]=2)[N:14]=1
Reactant: COc1cc(C(=O)O)ccc1Nc1nccc(-c2c(C)c3n(c2C)CCNC3=O)n1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: CN1CCC(N)CC1
Agent: F[B-](F)(F)F
Product: Cc1c(-c2ccnc(Nc3cccc(CCC(=O)N(C)C)c3)n2)c(C)n2c1C(=O)NCC2

Procedure:
By reaction of Example I-27 4-[4-(6,8-Dimethyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazin-7-yl)-pyrimidin-2-ylamino]-3-methoxy-benzoic acid and 4-amino-1-methylpiperidine as described above but using TBTU as the coupling agent.
Reaction SMILES: [C:1]([CH:3]([OH:18])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=1)#[N:2].[CH3:19][C:20]1([CH3:35])[C@@H:22](/[CH:23]=[CH:24]\[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C@H:21]1[C:32](O)=[O:33]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:19][C:20]1([CH3:35])[C@@H:22](/[CH:23]=[CH:24]\[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[C@H:21]1[C:32]([O:18][C@H:3]([C:1]#[N:2])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([O:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:5]=1)=[O:33]
Reactant: N#CC(O)c1ccc(F)c(Oc2ccccc2)c1
Reactant: CC(C)(C)OC(=O)/C=C\[C@H]1[C@@H](C(=O)O)C1(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)/C=C\[C@H]1[C@@H](C(=O)O[C@H](C#N)c2ccc(F)c(Oc3ccccc3)c2)C1(C)C
Temperature: 20 °C
Reaction time: 3 h
Yield: 93.9 %

Procedure:
A solution of 30 g of (RS)α-cyano-3-phenoxy-4-fluoro-benzyl alcohol, 300 mg of 4-dimethylamino-pyridine and 50 ml of methylene chloride was added all at once at -5° C. to a solution of 30 g of (1R,cis,Z) 2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylic acid in 100 ml of methylene chloride and the mixture was stirred at 0° C. for 30 minutes and at 20° C. for 3 hours. The mixture was filtered and the filtrate was evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with an 8-2 n-hexane-ethyl acetate mixture to obtain 53.9 g of (S)α-cyano-3-phenoxy-4-fluoro-benzyl (1R,cis,Z) 2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylate.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[C:5]([O:13][CH3:14])[CH:4]=1.[Br:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-][Cr](O[Cr]([O-])(=O)=O)(=O)=O>>[Br:15][C:16]1[CH:23]=[CH:22][C:19]([C:20]([C:3]2[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[C:5]([O:13][CH3:14])[CH:4]=2)=[O:21])=[CH:18][CH:17]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: COc1cc(Br)cc(OC)c1OC
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: [Mg]
Agent: c1cc[nH+]cc1
Product: COc1cc(C(=O)c2ccc(Br)cc2)cc(OC)c1OC

Procedure:
First, magnesium was added to 1-bromo-3,4,5-trimethoxybenzene as a starting material, as shown in Reaction 6, and then 4-bromobenzaldehyde was added thereto to obtain a compound. Thus obtained compound was oxidized using PDC to obtain a Compound 21 derivative [(4-bromophenyl)(3,4,5-trimethoxyphenyl)methanone]. Using thus obtained compound as a starting material aminothiazole was introduced in the same manner as in the synthesis of Compound 516 to obtain Compound 571 in a form of a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:7]=2[C:6]([C:16]2([C:27]#[N:28])[CH2:25][CH2:24][C:23]3[N:22]=[CH:21][NH:20][C:19](=[O:26])[C:18]=3[CH2:17]2)=[CH:5][CH:4]=1.[C:29](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C>[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:7]=2[C:6]([C:16]2([C:27]#[N:28])[CH2:25][CH2:24][C:23]3[N:22]=[CH:21][N:20]([CH3:29])[C:19](=[O:26])[C:18]=3[CH2:17]2)=[CH:5][CH:4]=1
Reactant: COc1ccc(C2(C#N)CCc3nc[nH]c(=O)c3C2)c2c1oc1ccccc12
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: COc1ccc(C2(C#N)CCc3ncn(C)c(=O)c3C2)c2c1oc1ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.9 %

Procedure:
To a well stirred slurry of compound obtained in example 13 (75 mg, 0.2 mmol) and cesium carbonate (73 mg, 0.22 mmol) in dry DMF (5 ml) was added iodomethane (36.92 mg, 0.26 mol) and the mixture was allowed to stir for 1 hr at room temperature under nitrogen atmosphere. The reaction mixture was quenched with ice water (50 ml), and then extracted with ethyl acetate (50 ml). The organic layer was washed with water followed by brine and dried over sodium sulfate. The organic layer was concentrated under vacuum and the crude product was purified by column chromatography to get 40 mg of the pure product (Yields-52%) MP-235.4-240.8° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([NH:23]C(=O)OC(C)(C)C)[CH2:18]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[CH2:13][CH2:14][F:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:39]>>[ClH:39].[NH2:23][C@@H:19]1[CH2:20][CH2:21][CH2:22][N:17]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:16])[CH2:13][CH2:14][F:15])[C:4]=23)[CH2:18]1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCN(c2c(Br)cnc3[nH]cc(NC(=O)CCF)c23)C1
Reactant: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cl
Product: N[C@@H]1CCCN(c2c(Br)cnc3[nH]cc(NC(=O)CCF)c23)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 38 %

Procedure:
(R)-tert-Butyl 1-(5-bromo-3-(3-fluoropropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (50 mg, 0.103 mmol) was placed in DCM (3 mL) at room temperature. TFA (1 mL) was then added, and the reaction was stirred at room temperature for 1 hour and concentrated to dryness. The residue was then purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-50% CH3CN/water). The resulting product was next dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirred solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give the product (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-fluoropropanamide hydrochloride (0.018 g, 38% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.24 (s, 1H), 7.29 (s, 1H), 4.77-4.73 (m, 1H), 4.66-4.65 m, 1H), 3.73-3.70 (m, 1H), 3.54-3.50 (m, 1H), 3.32-3.29 (m, 1H), 3.21-3.16 (m, 2H), 2.85-2.84 (m, 1H), 2.79-2.77 (m, 1H), 2.04-2.02 (m, 1H), 1.79-1.76 (m, 1H), 1.67-1.65 (m, 1H), 1.56-1.53 (m, 1H). LCMS (APCI+) m/z 384, 386 (M+H)+.
Reaction SMILES: [CH:1]1([CH2:7][C:8]([OH:10])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH2:12]([O:16][C:17](=[O:21])[C@H:18]([CH3:20])[NH2:19])[CH:13]([CH3:15])[CH3:14]>>[CH2:12]([O:16][C:17](=[O:21])[C@H:18]([CH3:20])[NH:19][C:8](=[O:10])[CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[CH:13]([CH3:15])[CH3:14]
Reactant: O=C(O)CC1CCCCC1
Reactant: CC(C)COC(=O)[C@H](C)N
Agent: Cl
Product: CC(C)COC(=O)[C@H](C)NC(=O)CC1CCCCC1

Procedure:
Following General Procedure B above, and using cyclohexylacetic acid (Aldrich) and L-alanine iso-butyl ester hydrochloride (from Example B above), the title compound was prepared as a solid having a melting point of 92° C.-93° C. The reaction was monitored by tlc on silica gel (Rf=0.39 in 1:3 EtOAc:hexane) and purification was by extraction with Et2O followed by washes with aqueous K2CO3 and aqueous HCl.