Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OC1C=CC(CNC(=O)C2C=CC(NC3C4[N:18]([CH:27]=[CH:28]N=4)[C:19]([C:22]4[CH:23]=[N:24]N[CH:26]=4)=CN=3)=CC=2)=CC=1.[Br:33][C:34]1[N:39]2[CH:40]=[CH:41][N:42]=[C:38]2[C:37]([NH:43][C:44]2[CH:52]=[CH:51][C:47]([C:48]([OH:50])=O)=[CH:46][CH:45]=2)=[N:36][CH:35]=1.NCC1C=NC=CC=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[Br:33][C:34]1[N:39]2[CH:40]=[CH:41][N:42]=[C:38]2[C:37]([NH:43][C:44]2[CH:45]=[CH:46][C:47]([C:48]([NH:24][CH2:23][C:22]3[CH:19]=[N:18][CH:27]=[CH:28][CH:26]=3)=[O:50])=[CH:51][CH:52]=2)=[N:36][CH:35]=1
Reactant: O=C(O)c1ccc(Nc2ncc(Br)n3ccnc23)cc1
Reactant: O=C(NCc1ccc(O)cc1)c1ccc(Nc2ncc(-c3cn[nH]c3)n3ccnc23)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: NCc1cccnc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCc1cccnc1)c1ccc(Nc2ncc(Br)n3ccnc23)cc1

Procedure:
In the same way as described for Compound 90, step 3, using 4-(5-bromoimidazo[1,2-a]pyrazin-8-ylamino) benzoic acid (365 mg, 1.57 mmol), 3-aminomethylpyridine (0.16 mL, 1.57 mmol), N,N-diisopropylethylamine (0.42 mL, 2.35 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (715 mg, 1.9 mmol) and DMF (6mL). The crude residue is purified using column chromatography, eluting with EtOAc followed by EtOAc:MeOH (95:5) then EtOAc:NH3 (7M in MeOH). The title amide is isolated as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[C:3]=1[OH:9].C(=O)(O)[O-].[Na+].Cl[CH2:16][C:17](Cl)=[O:18]>C(#N)C.O.CCOC(C)=O>[Br:8][C:4]1[C:3]2[O:9][CH2:16][C:17](=[O:18])[NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(Br)c1O
Reactant: O=C(Cl)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1COc2c(Br)cccc2N1
Temperature: 0 °C
Yield: 94 %

Procedure:
To a solution of 2-amino-6-bromophenol (1 g, 5.32 mmol) in acetonitrile (10 mL) and water (10 mL) was added sodium bicarbonate (1.028 g, 12.23 mmol). The mixture was cooled to 0° C. and chloroacetyl chloride (0.554 mL, 6.91 mmol) was added dropwise. The reaction was refluxed overnight. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water, dried over anhydrous MgSO4, filtered, and concentrated to afford the title compound (1.14 g, 94% yield) as a dark brown solid. 1H NMR (400 MHz, CDCl3) δ 8.22 (br. s, 1H), 7.23 (dd, J=8.0, 1.4 Hz, 1H), 6.86 (t, J=8.0 Hz, 1H), 6.76 (dd, J=7.9, 1.3 Hz, 1H), 4.74 (s, 2H).
Reaction SMILES: C([O:8][C:9]([C@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:36])[CH2:17][CH2:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[C:26]([O:28]CC1C=CC=CC=1)=[O:27])=[O:20])=[O:10])C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[C:26]([C@H:22]1[CH2:23][CH2:24][CH2:25][N:21]1[C:19](=[O:20])[CH2:18][CH2:17][C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C@@H:11]1[C:9]([OH:10])=[O:8])=[O:36])([OH:28])=[O:27]
Reactant: O=C(OCc1ccccc1)[C@H]1CCCN1C(=O)CCC(=O)N1CCC[C@@H]1C(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: O=C(O)[C@H]1CCCN1C(=O)CCC(=O)N1CCC[C@@H]1C(=O)O
Yield: 108.9 %

Procedure:
A solution of 256 mg (0.5 mmol) (R)-1-[4-[(R)-2-benzyloxycarbonyl-pyrrolidin-1-yl]-4-oxo-butyryl]-pyrrolidine-2-carboxylic acid benzyl ester in 5 ml ethanol was stirred with 13 mg 10% Palladium on carbon under 1 atm of hydrogen for 16 h at room temperature. After filtration to remove the catalyst, concentration in vacuo afforded 170 mg (100%) of the title compound KR)-1[4-[( R)-2-carboxy-pyrrolidin-1-yl]-4-oxo-butyryl]-pyrrolidine-2-carboxylic acid as a colorless viscous oil.
Reaction SMILES: [CH:1]12[C:9](=[O:10])[CH:6]([CH2:7][CH2:8]1)[CH2:5][CH:4]=[CH:3][CH2:2]2.[CH2:11](O)[CH2:12][OH:13]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:10]1[CH2:11][CH2:12][O:13][C:9]21[CH:6]1[CH2:7][CH2:8][CH:1]2[CH2:2][CH:3]=[CH:4][CH2:5]1
Reactant: OCCO
Reactant: O=C1C2CC=CCC1CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: C1=CCC2CCC(C1)C21OCCO1
Temperature: 25 °C
Yield: 99.7 %

Procedure:
A mixture of bicyclo[4.2.1]non-3-en-9-one (10 g, 73 mmol), ethyleneglycol (12.3 ml, 220 mmol) and p-toluenesulphonic acid monohydrate (100 mg) in toluene (250 ml) was refluxed in a Dean-Stark apparatus for four hours. The reaction mixture was cooled to ambient temperature and sequentially washed with water (3×50 ml) and brine (100 ml). The organic extract was dried over MgSO4 and concentrated in vacuo, to afford spiro[bicyclo[4.2.1]non-3-ene-9,2′-[1,3]dioxolane] (13.12 g, 99.5%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]=O)=[N:6][CH:7]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1>ClCCCl.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[N:6][CH:7]=1
Reactant: O=Cc1ccc(Br)cn1
Reactant: C1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Product: Brc1ccc(CN2CCCC2)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2 g of 5-bromo-2-formylpyridine in 20 mL of 1,2-dichloroethane are successively added, under argon, 4.55 g of sodium triacetoxyborohydride and 0.94 mL of pyrrolidine. The reaction mixture is stirred at room temperature for 1 hour and then diluted with dichloromethane and the organic phase is washed with saturated sodium hydrogen carbonate solution, with water and with saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (98/2 by volume) to give 0.93 g of 5-bromo-2-pyrrolidin-1-ylmethylpyridine, the characteristics of which are as follows:
Reaction SMILES: F[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH3:8])[CH:7]=1.[F:12][C:13]1[CH:14]=[CH:15][C:16]([OH:21])=[C:17]([CH:20]=1)[C:18]#[N:19].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C>[F:12][C:13]1[CH:14]=[CH:15][C:16]([O:21][C:3]2[CH:2]=[CH:7][C:6]([CH3:8])=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=2)=[C:17]([CH:20]=1)[C:18]#[N:19]
Reactant: N#Cc1cc(F)ccc1O
Reactant: Cc1cc(F)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: Cc1ccc(Oc2ccc(F)cc2C#N)cc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 8 h
Yield: 95.1 %

Procedure:
In a 3-necked 5 L flask, equipped with a mechanic stirrer, a condenser, and a J-Kem temperature probe, a solution of 5-fluoro-2-nitrotoluene (158 g, 1.02 mol) in N,N-dimethylacetamide (500 mL) was added to a mixture of 5-fluoro-2-hydroxybenzonitrile (147 g, 1.07 mol) and potassium carbonate (163 g, 1.2 mol) in N,N-dimethylacetamide (573 mL) at room temperature. The mixture was heated to 100° C. After 8 hours, the reaction mixture was cooled to room temperature and water (3400 mL) was added in an ice bath. The precipitate was filtered, washed with water (1073 mL×2), and dried in vacuum (40° C.) to give (264 g, 90%) of the desired compound as a brown solid. MS (APCI−) m/z 272 (M−1) was detected. 1H NMR (400 MHz, CDCl3) δ 8.10 (d, 1H, J=9 Hz), 7.41-7.48 (m, 1H), 7.38 (m, 1H), 7.07-7.14 (m, 1H), 6.88-7.10 (m, 1H), 2.63 (s, 3H).