Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[CH2:3]([C:5]1[CH:32]=[CH:31][C:8]([C:9]([N:11]2[CH2:30][CH2:29][C:14]3([C:19]4=[CH:20][CH:21]=[CH:22][N:18]4[C:17]4[CH:23]=[CH:24][C:25]([C:27]#[N:28])=[CH:26][C:16]=4[O:15]3)[CH2:13][CH2:12]2)=[O:10])=[CH:7][C:6]=1[O:33][CH3:34])[CH3:4]>CO.O.O.O.O.O.O.Cl[Co]Cl>[NH2:28][CH2:27][C:25]1[CH:24]=[CH:23][C:17]2[N:18]3[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]3([CH2:29][CH2:30][N:11]([C:9]([C:8]4[CH:31]=[CH:32][C:5]([CH2:3][CH3:4])=[C:6]([O:33][CH3:34])[CH:7]=4)=[O:10])[CH2:12][CH2:13]3)[O:15][C:16]=2[CH:26]=1
Reactant: CCc1ccc(C(=O)N2CCC3(CC2)Oc2cc(C#N)ccc2-n2cccc23)cc1OC
Agent: Cl[Co]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCc1ccc(C(=O)N2CCC3(CC2)Oc2cc(CN)ccc2-n2cccc23)cc1OC
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
NaBH4 (17.7 mg, 0.47 mmol) was slowly added to a solution of 1-(4-ethyl-3-methoxy-benzoyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-7′-carbonitrile (20 mg, 0.050 mmol) and dichlorocobalt hexahydrate (22 mg, 0.090 mmol) in MeOH (1 mL) and was stirred at room temperature for 10 minutes. The reaction mixture was filtered and purified by reverse phase LC-MS (10-99% CH3CN/H2O) to yield (7-(aminomethyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)(4-ethyl-3-methoxyphenyl)methanone. ESI-MS m/z calc. 431.5. found 432.5 (M+1)+; Retention time: 1.44 minutes (3 min run).
Reaction SMILES: [F:1][C:2]1[CH:37]=[CH:36][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])[S:17]([C:20]3[CH:25]=[CH:24][C:23](C=O)=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.Cl.[OH:39][NH2:40].C(=O)([O-])[O-].[Na+].[Na+].O>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([CH:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][N:16]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])[S:17]([C:20]3[CH:21]=[CH:22][C:23](=[N:40][OH:39])[CH2:24][CH:25]=3)(=[O:19])=[O:18])[CH2:12][CH2:13]2)=[O:7])=[CH:36][CH:37]=1
Reactant: NO
Reactant: COc1ccccc1N(CCN1CCC(C(=O)c2ccc(F)cc2)CC1)S(=O)(=O)c1ccc(C=O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccccc1N(CCN1CCC(C(=O)c2ccc(F)cc2)CC1)S(=O)(=O)C1=CCC(=NO)C=C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 102.7 %

Procedure:
N-{2-[4-(4-Fluorobenzoyl)piperidino]ethyl}-4-formyl-N-(2-methoxyphenyl)benzenesulfonamide (63 mg, 0.12 mmol) and hydroxyamine hydrochloride (9.5 mg, 0.132 mmol) were dissolved in ethanol (2 ml) to which were subsequently added anhydrous sodium carbonate (14 mg, 0.132 mmol) and water (1 ml). After 1.5 hours of stirring at room temperature, ethanol was removed by evaporation, and the resulting residue was mixed with water (10 ml) to collect crystals by filtration. The thus collected crystals were washed with water and hexane, dissolved in methylene chloride (50 ml) and then dried on anhydrous sodium carbonate. Thereafter, the solvent was removed by evaporation to obtain 65 mg (100%) of the title compound in the form of colorless powder.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[O:8][C:6](=O)[C:5]2=[CH:11][C:12]=1[CH3:13].[NH2:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.O>C(O)(=O)C>[CH3:13][C:12]1[CH:11]=[C:5]2[C:4](=[CH:3][C:2]=1[CH3:1])[C:9](=[O:10])[N:14]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[C:6]2=[O:8]
Reactant: Nc1cccnc1
Reactant: Cc1cc2c(cc1C)C(=O)OC2=O
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc2c(cc1C)C(=O)N(c1cccnc1)C2=O
Yield: 82.9 %

Procedure:
4,5-dimethylphthalic anhydride (2.0 g, 11 mmol) and 3-aminopyridine (1.0 g, 11 mmol) were heated under reflux in acetic acid (30 ml) for 1.5 hrs. After standing to cool, water was added thereto, the precipitated crystals were collected by filtration, washed with water, followed by drying to give 2.3 g of 5,6-dimethyl-2-(3-pyridyl)isoindolin-1,3-dione.
Reaction SMILES: [C:1]([OH:4])(=O)[CH3:2].Cl[CH:6]1[C:14]2[C:9](=CC=[CH:12][CH:13]=2)[C:8]2([CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:7]1>[O-2].[O-2].[O-2].[Cr+6].O>[C:8]12([CH2:15][CH2:16][CH2:17][CH2:18]1)[C:7]1[C:2](=[CH:12][CH:13]=[CH:14][CH:6]=1)[C:1](=[O:4])[CH2:9]2
Reactant: CC(=O)O
Reactant: ClC1CC2(CCCC2)c2ccccc21
Agent: [Cr+6]
Agent: [O-2]
Solvent: O
Product: O=C1CC2(CCCC2)c2ccccc21

Procedure:
To a mixture of acetic acid (75 ml), water (75 ml) and chromium trioxide (75 g; 0.75 moles) there are added dropwise under agitation 3'-chlorospiro(cyclopentane-1,1'-indan) (103 g; 0.5 moles), the temperature being held at 30°-40° C. by external cooling.
Reaction SMILES: O[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13]C=2)(C)C)=[CH:4][CH:3]=1.CC(C1C=CC(OCC2OC2)=CC=1)(C1C=CC([O:27]CC2OC2)=CC=1)C.C(P(CCCC)CCCC)CCC>>[CH:7]1[CH:6]=[C:5]([C:8]2[CH:11]=[CH:16][CH:15]=[C:14]([OH:17])[CH:13]=2)[C:4]([OH:27])=[CH:3][CH:2]=1
Reactant: CC(C)(c1ccc(OCC2CO2)cc1)c1ccc(OCC2CO2)cc1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: CCCCP(CCCC)CCCC
Product: Oc1cccc(-c2ccccc2O)c1

Procedure:
152 g of bisphenol A, 63 g of a diglycidyl ether of bisphenol A having an epoxy equivalent weight of 189 and 0.1 g of tributylphosphine were heated at 160° C. for 1 hour. Afterwards the epoxy was no longer detectable, and a chain-extending diphenol had formed. 53.8 g of isopropanol, 129 g of di-n-butylamine, 31.5 g of paraformaldehyde and 17.6 g of isobutanol were added and the mixture was heated at 80° C. for 2 hours. The product had a solids content of 80% by weight.
Reaction SMILES: CN(C)CCCOC1C=CC(C2SC(NC3C=CC=CC=3)=NC=2)=CC=1.[S:26]1[CH:30]=[CH:29][C:28]([C:31]2[S:35][C:34]([NH:36][C:37]3[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][C:38]=3[C:44]([F:47])([F:46])[F:45])=[N:33][CH:32]=2)=[CH:27]1.Cl.Cl[CH2:50][CH2:51][N:52]([CH:56]([CH3:58])[CH3:57])[CH:53]([CH3:55])[CH3:54]>C(Cl)Cl.CO>[CH:53]([N:52]([CH:56]([CH3:58])[CH3:57])[CH2:51][CH2:50][O:43][C:40]1[CH:41]=[CH:42][C:37]([NH:36][C:34]2[S:35][C:31]([C:28]3[CH:29]=[CH:30][S:26][CH:27]=3)=[CH:32][N:33]=2)=[C:38]([C:44]([F:47])([F:46])[F:45])[CH:39]=1)([CH3:55])[CH3:54]
Reactant: CC(C)N(CCCl)C(C)C
Reactant: Oc1ccc(Nc2ncc(-c3ccsc3)s2)c(C(F)(F)F)c1
Agent: CN(C)CCCOc1ccc(-c2cnc(Nc3ccccc3)s2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CC(C)N(CCOc1ccc(Nc2ncc(-c3ccsc3)s2)c(C(F)(F)F)c1)C(C)C

Procedure:
The title compound is prepared as described in Example 8 for {5-[4-(3-dimethylamino-propoxy)-phenyl]-thiazol-2-yl}phenyl-amine but starting from 4-(5-thiophen-3-yl-thiazol-2-ylamino)-3-trifluoromethyl-phenol (Example 28) and using (2-chloroethyl)-diisopropylamine hydrochloride. The title compound: ES-MS: 469.9 [M+H]+; single peak at tR=3.67 min (System 2); Rf=0.38 (CH2Cl2/MeOH, 90/10).
Reaction SMILES: Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Mg]Br)C.[F:16][C:17]1[C:26]([CH:27]=[O:28])=[C:25]([F:29])[CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][CH:21]=[N:22]2>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:27]([C:26]3[C:17]([F:16])=[C:18]4[C:23](=[CH:24][C:25]=3[F:29])[N:22]=[CH:21][CH:20]=[CH:19]4)[OH:28])=[CH:3][N:4]=2)[N:7]=1
Reactant: O=Cc1c(F)cc2ncccc2c1F
Reactant: Clc1ccc2ncc(Br)n2n1
Agent: CC[Mg]Br
Solvent: C1CCOC1
Product: OC(c1c(F)cc2ncccc2c1F)c1cnc2ccc(Cl)nn12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
3-Bromo-6-chloro-imidazo[1,2-b]pyridazine (4.40 g, 18.95 mmol) was dissolved THF (189 mL) and under nitrogen conditions, ethylmagnesium bromide solution (3 M, 6.32 mL) was added slowly. The RM was stirred at rt for 15 min then a solution of 5,7-difluoro-quinoline-6-carbaldehyde (Intermediate F, 3.66 g, 18.95 mmol) in THF was added. It was stirred at rt for 30 min. The reaction was quenched with 10% NH4Cl. The precipitate was filtered off and a first part of the title compound was obtained as a white solid. The filtrate was concentrated and was taken up with 10% NH4Cl. The precipitate was filtered off and was washed with EtOAc. A second part of the title compound was obtained as a brown solid (tR 0.8 min (conditions 2), MH+=347).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([Br:11])=[CH:6][C:5]=1[CH3:12].[Br:14]NC(=O)CCC(N)=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:5]([CH3:12])=[CH:6][C:7]([Br:11])=[CH:8][C:9]=1[CH2:10][Br:14]
Reactant: NC(=O)CCC(=O)NBr
Reactant: COC(=O)c1c(C)cc(Br)cc1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1c(C)cc(Br)cc1CBr

Procedure:
A mixture of 4-bromo-2,6-dimethyl-benzoic acid methyl ester (3.4 g, 14.2 mmol), N-bromosuccinamide (2.5 g, 14.2 mmol), and benzoyl peroxide (0.060 g, 0.25 mmol) in carbon tetrachloride (50 mL) was heated at reflux until majority of ester was consumed (as analyzed by GC/MS). The resulting mixture was filtered and the filtrate concentrated to afford 4-bromo-2-bromomethyl-6-methyl-benzoic acid methyl ester. The product obtained was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25]([CH:27]=O)=[CH:26][C:4]=2[N:3]=1.C(OP([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])(OCC)=O)C>>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=3[CH3:22])=[CH:7][C:6]=2[C:5]2[CH:23]=[CH:24][C:25](/[CH:27]=[CH:37]/[C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:26][C:4]=2[N:3]=1
Reactant: COc1ccc(CCc2cnc3c(N)nc4cc(C=O)ccc4c3c2)c(C)c1
Reactant: CCOC(=O)CP(=O)(OCC)OCC
Product: CCOC(=O)/C=C/c1ccc2c(c1)nc(N)c1ncc(CCc3ccc(OC)cc3C)cc12

Procedure:
(E)-ethyl 3-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)acrylate was prepared from 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (from Example 69) and ethyl 2-(diethoxyphosphoryl)acetate (commercially available) following the procedures described for Example 65/Step 3. LRMS [M+H]=442.2
Reaction SMILES: [C:1]([C:4]1[CH:19]=[CH:18][C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[O:9])=[C:6]([NH:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[N:5]=1)(=[NH:3])[NH2:2].[N:30]#[C:31]Br.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:31]([NH:3][C:1]([C:4]1[CH:19]=[CH:18][C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[O:9])=[C:6]([NH:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[N:5]=1)=[NH:2])#[N:30]
Reactant: N=C(N)c1ccc(C(=O)NCc2cccnc2)c(NCCc2cccc(F)c2)n1
Reactant: N#CBr
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: N#CNC(=N)c1ccc(C(=O)NCc2cccnc2)c(NCCc2cccc(F)c2)n1
Yield: 40.9 %

Procedure:
A mixture of 6-carbamimidoyl-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide (0.013 g, 0.034 mmol), CNBr (3N, 0.017 mL, 0.051 mmol), DIPEA (0.0085 mL, 0.051 mmol), in DCM (0.10 mL) was stirred at room temperature until the reaction was complete. The reaction mixture was concentrated to dryness and purified by RP-HPLC using a mixture of acetonitrile and H2O to give 6-(N-cyanocarbamimidoyl)-2-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide as a solid (0.0058 g, 41%). LC/MS (M+H+) m/z 418.1.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][CH2:7][C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[OH-].[K+].[CH2:15](Br)[CH:16]=[CH2:17].O>C(O)C>[CH2:17]([O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8](=[O:10])[CH3:9])=[CH:11][CH:12]=1)[CH:16]=[CH2:15]
Reactant: C=CCBr
Reactant: CC(=O)CCc1ccc(O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C=CCOc1ccc(CCC(C)=O)cc1

Procedure:
p-Hydroxy benzylacetone (1.5 g.), KOH (6 g.) and allyl bromide (1.2 g.) were stirred in ethanol (50 ml) overnight. Water was added and the mixture extracted with ether, which was evaporated to give the compound (1.6 g.) as an oil purified by column chromatography.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]([C:16]([OH:18])=O)[NH:15][C:11]=3[N:10]=[CH:9]2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.CCN(C(C)C)C(C)C.[CH3:40][O:41][CH2:42][CH2:43][NH2:44]>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]3[CH:13]=[C:14]([C:16]([NH:44][CH2:43][CH2:42][O:41][CH3:40])=[O:18])[NH:15][C:11]=3[N:10]=[CH:9]2)=[CH:6][CH:7]=1
Reactant: COCCN
Reactant: O=C(O)c1cc2c(ncn2-c2ccc(Br)cc2)[nH]1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COCCNC(=O)c1cc2c(ncn2-c2ccc(Br)cc2)[nH]1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A mixture of 1-(4-bromophenyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylic acid (70 mg, 0.23 mmol), CDI (75 mg, 0.46 mmol) and DIPEA (0.1 mL) in dry THF (3 mL) was stirred at 60° C. for 1 h and then treated with 2-methoxyethylamine (0.1 mL). After additional 2 h at 60° C., the mixture was concentrated under reduced pressure, the residue suspended in water (5 mL) and the solid collected by filtration and washed with water to give 1-(4-bromophenyl)-N-(2-methoxyethyl)-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxamide EXAMPLE 3. LC-MS (ES+): m/z 363/365 (1/1) [MH+]. 1H NMR (CDCl3, 400 MHz): δ=3.41 (s, 3H), 3.57 (t, J=4.9 Hz, 2H), 3.67 (app. q, J=4.9 Hz, 2H), 6.34 (br s, 1H, CONH), 6.60 (s, 1H), 7.42 (d, J=8.7 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.88 (s, 1H), 9.32 (br s, 1H, NH).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([NH2:12])=[O:11].Cl[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][C:21]([NH2:23])=O>>[C:20]1([C@H:9]2[C@H:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:10](=[O:11])[NH:12][C:10]2=[O:11])[C:15]2=[C:16]3[C:17](=[CH:18][CH:19]=[CH:14]2)[CH2:7][CH2:2][CH2:3][N:23]3[CH:21]=1
Reactant: NC(=O)Cc1ccccc1Cl
Reactant: NC(=O)Cc1ccc(F)cc1Cl
Product: O=C1NC(=O)[C@@H](c2cn3c4c(cccc24)CCC3)[C@@H]1c1ccccc1Cl

Procedure:
(±)-Trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1yl)-4-(2-chlorophenyl)-pyrrolidine-2,5-dione was prepared according to Example 40 replacing 2-chloro-4-fluorophenylacetamide with 2-chlorophenylacetamide. 1H NMR (DMSO-d6) 400 MHz δ: 11.655 (s, 1H), 7.41-7.48 (m, 2H), 7.27-7.35 (m, 3H, J=7.2), 7.87 (d, 1H, J=7.6), 6.81-6.88 (m, 2H), 4.632 (d, 1H, J=7.6 Hz), 4.494 (d, 1H, J=7.2), 4.07-4.10 (m, 2H), 2.884 (m, 2H), 2.09 (m, 2H).