Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12](=[C:17]1[CH2:20][O:19][CH2:18]1)[C:13]([O:15][CH3:16])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C>CO.[Pd]>[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH:17]1[CH2:20][O:19][CH2:18]1)[C:13]([O:15][CH3:16])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)C(NC(=O)OCc1ccccc1)=C1COC1
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)C(NC(=O)OCc1ccccc1)C1COC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 42.8 %

Procedure:
Pd/C (10%, 5.0 g) was added to a solution of methyl 2-(benzyloxycarbonylamino)-2-(oxetan-3-ylidene)acetate (10.0 g, 36 mmol) in MeOH (100 mL). The suspension was stirred under hydrogen atmosphere at ambient temperature for 12 h. The catalyst was filtered off and washed with MeOH (100 mL). The filtrate and washings were combined followed by addition of benzyloxycarbonyl N-succinimide (Cbz-OSu; 10.0 g, 40 mmol) and triethylamine (15.2 mL, 108 mmol). The reaction mixture was stirred for 12 h at ambient temperature and then concentrated. The residue was purified by flash column chromatography on silica gel (Hexane/EtOAc=5:1) to afford methyl 2-(benzyloxycarbonylamino)-2-(oxetan-3-yl)acetate (4.3 g, 41% yield) as a yellow solid.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1.[CH3:12][NH:13][C@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15]>CN1C(=O)CCC1>[CH3:12][N:13]([C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1
Reactant: Cc1nnc2ccc(Cl)nn12
Reactant: CN[C@@H](C)c1ccccc1
Solvent: CN1CCCC1=O
Product: Cc1nnc2ccc(N(C)[C@H](C)c3ccccc3)nn12
Temperature: 200 °C

Procedure:
6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine (120 mg, 0.712 mmol; commercially available or prepared according to patent WO2006/039325A2), (S)-N-methyl-1-phenylethanamine (385 mg, 2.85 mmol) and anhydrous NMP (1 mL) were charged into a microwave tube equipped with a magnetic stirbar. After the vessel was sealed, the mixture was heated at 200° C. for 60 min using microwave irradiation. The reaction was purified by normal phase chromatography (10% CH2Cl2 in hexane then a gradient of 0% to 20% MeOH in CH2Cl2) and by reverse phase chromatography before being lyophilized to give the (S)-N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 3) as an off-white solid (69 mg; 36% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.01 (d, J=10.1 Hz, 1H), 7.25-7.39 (m, 6H), 5.71 (q, J=6.9 Hz, 1H), 2.84 (s, 3H), 2.54 (s, 3H), 1.58 (d, J=6.9 Hz, 3H). LRMS [M+H]+: 268 m/z.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]([CH3:14])[NH:11][CH:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:17]1[N:22]=[CH:21][CH:20]=[CH:19][N:18]=1>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]([CH3:14])[N:11]([C:17]2[N:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]([CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Clc1ncccn1
Reactant: CC1CN(C(=O)OC(C)(C)C)CC(C)N1
Solvent: O
Product: CC1CN(C(=O)OC(C)(C)C)CC(C)N1c1ncccn1
Reaction time: 0.5 h
Yield: 18.2 %

Procedure:
3,5-Dimethylpiperazine-1-carboxylic acid tert-butyl ester (1.676 g) and 2-chloropyrimidine (716 mg) were combined, melted in an oil bath at 120° C., and stirred for 5 hr 30 min. Water (10 ml) was added and the mixture was stirred, extracted with ethyl acetate (30 ml), and washed with saturated brine. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (Yamazen HI-FLASH™ COLUMN size L, elution solvent: hexane/ethyl acetate) to give the title compound (333 mg).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([O:14]C)=[O:13])[CH:8]=[CH:9][CH:10]=1.[OH-].[Na+].Cl>CO>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([OH:14])=[O:13])[CH:8]=[CH:9][CH:10]=1
Reactant: COC(=O)Cc1cccc(OCCCl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)Cc1cccc(OCCCl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92 %

Procedure:
Methyl 3-(2-chloro-ethoxy)-phenylacetate (7.0 g, 32.9 mmol) was dissolved in methanol (40 mL) and 6N NaOH (5.5 mL) was added. The mixture was stirred at room temperature overnight then acidified by addition of 6N hydrochloric acid (5.5 mL). A white precipitate formed which was filtered, washed with 1N HCl, water and dried to afford 3-(2-chloroethoxy)-phenylacetic acid (6.5 g, 99%). 1H NMR (CDCl3) δ3.55 (s, 2H), 3.75 (t, 2H), 4.15 (t, 2H), 6.78 (dd, 1H), 6.80 (d, 1H), 6.84 (dd, 1H), 7.16 (dd, 1H).
Reaction SMILES: Cl[C:2]1[C:3]([F:22])=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[O:21].[N:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1>>[N:23]1[CH:28]=[CH:27][C:26]([C:2]2[C:3]([F:22])=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]3=[O:21])=[CH:25][CH:24]=1
Reactant: OB(O)c1ccncc1
Reactant: CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O
Product: CCOC(=O)c1cc(C2CC2)c2c(C)c(-c3ccncc3)c(F)cn2c1=O

Procedure:
Ethyl 8-(pyridin-4-yl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A from ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.34 mmol) and pyridin-4-yl-boronic acid (52.1 mg, 0.42 mmol). Purification by flash silica column chromatography (DCM:MeOH) (1:0 to 9:1) afforded quantitatively the title compound as a yellow solid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1.C([O-])(O)=O.[Na+].[CH3:15][CH:16]([CH3:21])[CH2:17][C:18](Cl)=[O:19]>O.C1COCC1>[CH3:15][CH:16]([CH3:21])[CH2:17][C:18]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1)=[O:19]
Reactant: CC(C)CC(=O)Cl
Reactant: O=C(O)[C@@H]1CCCNC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)CC(=O)N1CCC[C@@H](C(=O)O)C1
Reaction time: 8 h
Yield: 76.6 %

Procedure:
To a solution of (R)-piperidine-3-carboxylic acid (2.0 g, 15.48 mmol) in water (40 mL) and THF (20 mL) were added NaHCO3 (3.30 g, 38.70 mmol) and 3-methylbutanoyl chloride (2.8 mL, 23.2 mmol) at room temperature. The reaction was stirred overnight, concentrated under reduced pressure, diluted with water (50 mL) and extracted with EtOAc (1×). The aqueous layer was acidified with 1N HCl, extracted with EtOAc (3×) and the combined extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (2.53 g, 76%). MS 214 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:13]=3[N:14]=2)[CH:5]=1.[Br:21]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][Br:21])[C:13]=3[N:14]=2)[CH:5]=1
Reactant: COC(=O)c1cccc(-c2nc3c(C)cccc3o2)c1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cccc(-c2nc3c(CBr)cccc3o2)c1

Procedure:
A solution of 3-(4-methyl-benzooxazol-2-yl)-benzoic acid methyl ester (1.2 mmol), N-bromo succinimide (1.5 mmol) and AIBN (0.3 mmol) in CCl4 are heated in microwave at 100° C. for 30 minutes (1 mL). The mixture is filtered and concentrated to yield the crude 3-(4-bromomethyl-benzooxazol-2-yl)-benzoic acid methyl ester. LC/MS (ES+): (M+) 346.1, 348.1, (M-Br) 266.1, 268.1.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.Cl[CH2:9][C:10]1[NH:11][C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[N:14]=1>>[N:11]1[C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[NH:14][C:10]=1[CH2:9][N:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1
Reactant: ClCc1nc2ccccc2[nH]1
Reactant: O=C1CCNCC1
Product: O=C1CCN(Cc2nc3ccccc3[nH]2)CC1

Procedure:
1-(2-Benzimidazolyl)methyl-4-piperidone is prepared from 4-piperidone and 2-(chloromethyl)benzimidazole essentially as described above in Example 38, Scheme C, step a.
Reaction SMILES: C(OC([N:11]1[CH:18]2[CH2:19][CH:14]3[CH2:15][CH:16]([CH2:21][CH:12]1[CH2:13]3)[CH:17]2Br)=O)C1C=CC=CC=1.C(O)C.[H][H]>[Pd].C(N(CC)CC)C>[CH:12]12[CH2:21][CH:16]3[CH2:15][CH:14]([CH2:19][CH:18]([CH2:17]3)[NH:11]1)[CH2:13]2
Reactant: [H][H]
Reactant: O=C(OCc1ccccc1)N1C2CC3CC(C2)C(Br)C1C3
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCO
Product: C1C2CC3CC1CC(C2)N3

Procedure:
To 1.0 g of N-benzyloxycarbonyl-4-bromo-2-azaadamantane, 10 g of ethanol, 0.32 g of triethylamine and 0.5 g of 10 wt % Pd/C (containing 50% of water) were charged, followed by stirring at 20 to 30° C. for 5 hours while 0.5 MPa of a hydrogen pressure was applied. Filtration by Celite (registered trademark by Celite Corporation) was carried out to remove a solid, and the mother liquor was quantitatively analyzed, whereupon the yield of 2-azaadamantane was 85%.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[Br:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH:22]=1)[C:18]([O:20][CH3:21])=[O:19]>C(Cl)Cl>[Br:12][C:13]1[CH:14]=[N+:15]([O-:9])[CH:16]=[C:17]([CH:22]=1)[C:18]([O:20][CH3:21])=[O:19]
Reactant: COC(=O)c1cncc(Br)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COC(=O)c1cc(Br)c[n+]([O-])c1
Temperature: 25 °C
Reaction time: 96 h
Yield: 33.1 %

Procedure:
A solution of mCPBA (70%, 4.46 g, 18.11 mmol) in DCM (100 ml) was added to a solution of methyl 5-bromonicotinate (3.11 g, 15.09 mmol) in DCM (100 ml). After stirring at room temperature for several hours, additional mCPBA (6.6 g, 26.77 mmol) was added (in portions) to drive the reaction to completion. After 4 days, the reaction mixture was sequentially washed with a saturated solution of sodium bicarbonate followed by water. The organic phase was dried over MgSO4, and concentrated to dryness. The crude material was purified by chromatography on silica gel using 50% EtOAc/hexanes to 100% EtOAc to give 1.16 g of the title product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.[Cl:18][C:19]1[N:24]=[CH:23][C:22]([C:25](O)=[O:26])=[CH:21][CH:20]=1>>[Cl:18][C:19]1[N:24]=[CH:23][C:22]([C:25]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)=[O:26])=[CH:21][CH:20]=1
Reactant: O=C(O)c1ccc(Cl)nc1
Reactant: CN1CCC(c2c[nH]c3ccc(N)cc23)CC1
Product: CN1CCC(c2c[nH]c3ccc(NC(=O)c4ccc(Cl)nc4)cc23)CC1
Yield: 39.8 %

Procedure:
Beginning with 7.0 mg (0.03 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole and 14.2 mg (0.09 mMol) 6-chloropyridine-3-carboxylic acid, 4.4 mg (40%) of the title compound were recovered.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]([N:15]=[N:16][C:17]2[CH:18]=[CH:19][C:20]([OH:27])=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[CH:22]=2)[CH:8]=[C:9]([C:11]([O:13]C)=[O:12])[CH:10]=1)=[O:4].[OH-].[Na+].C(O)C.Cl>O>[C:11]([C:9]1[CH:8]=[C:7]([N:15]=[N:16][C:17]2[CH:18]=[CH:19][C:20]([OH:27])=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[CH:22]=2)[CH:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:10]=1)([OH:13])=[O:12]
Reactant: COC(=O)c1cc(N=Nc2ccc(O)c(CC(=O)O)c2)cc(C(=O)OC)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)Cc1cc(N=Nc2cc(C(=O)O)cc(C(=O)O)c2)ccc1O

Procedure:
12 g of 5-(3,5-bis-(methoxycarbonyl)-phenylazo)-2-hydroxyphenylacetic acid, 350 ml of water and 7 g of sodium hydroxide were boiled for 1 hour. 50 ml of ethanol was added, and the solution was diluted with water to 500 ml. The hot solution was acidified with hydrochloric acid to pH 2 and cooled. The crystals were filtered off, washed with water and dried.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:16][CH:15]3[CH:11]([CH2:12][NH:13][CH2:14]3)[CH2:10]2)=[N:7][CH:8]=1.[CH3:19][C:20]1[CH:24]=[CH:23][O:22][C:21]=1[C:25](O)=[O:26]>>[CH3:19][C:20]1[CH:24]=[CH:23][O:22][C:21]=1[C:25]([N:13]1[CH2:14][CH:15]2[CH:11]([CH2:10][N:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:17])[F:18])=[CH:8][N:7]=3)[CH2:16]2)[CH2:12]1)=[O:26]
Reactant: FC(F)(F)c1ccc(N2CC3CNCC3C2)nc1
Reactant: Cc1ccoc1C(=O)O
Product: Cc1ccoc1C(=O)N1CC2CN(c3ccc(C(F)(F)F)cn3)CC2C1

Procedure:
The title compound was prepared in a manner analogous to Example 15, utilizing 2-(5-(trifluoromethyl)pyridin-2-yl)octahydropyrrolo[3,4-c]pyrrole and 3-methylfuran-2-carboxylic acid. MS (ESI) mass calcd. C18H18F3N3O2, 365.36; m/z found 366.0 [M+H]+. 1H NMR (CDCl3): 8.39 (s, 1H), 7.62 (d, J=9.1 Hz, 1H), 7.32 (d, J=1.4 Hz, 1H), 6.39 (d, J=8.8 Hz, 1H), 6.32 (d, J=1.4 Hz, 1H), 4.17 (brs, 1H), 3.94 (brs, 1H), 3.81 (brs, 3H), 3.71-3.67 (m, 1H), 3.50 (brs, 2H), 3.11 (brs, 2H), 2.37 (s, 3H).
Reaction SMILES: Br[C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=2)[S:4][C:3]=1[CH:16]1[O:20]CCO1.C[O:22][C:23]1[CH:24]=[CH:25][C:26]([CH3:32])=[C:27](B(O)O)[CH:28]=1>>[OH:22][C:23]1[CH:28]=[CH:27][C:26]([CH3:32])=[C:25]([C:2]2[C:6]([CH3:7])=[C:5]([C:8]3[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=3)[S:4][C:3]=2[CH:16]=[O:20])[CH:24]=1
Reactant: COc1ccc(-c2sc(C3OCCO3)c(Br)c2C)cc1
Reactant: COc1ccc(C)c(B(O)O)c1
Product: Cc1ccc(O)cc1-c1c(C=O)sc(-c2ccc(O)cc2)c1C
Yield: 50.4 %

Procedure:
Starting from 2-[3-bromo-5-(4-methoxyphenyl)-4-methylthien-2-yl]-1,3-dioxolane (1.1 g, 3.0 mmol, made in Example 1, Step 1) and substituting 5-methoxy-2-methylphenylboronic acid (0.55 g, 3.3 mmol) in place of 3-methoxyphenylboronic acid (Step 2), the title compound (0.49 g, 89%, m.p. 204-07° C.) was synthesized in essentially the same manner as described in Example 1, Steps 2-4.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9].[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1B(O)O>C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[C:2]1[N:3]=[C:4]([CH2:21][CH3:22])[C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[CH2:8][CH3:9]
Reactant: CCc1nc(N[C@@H]2c3ccccc3C[C@@H]2O)c(CC)nc1Br
Reactant: OB(O)c1ccc(Cl)cc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Product: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1c2ccccc2C[C@@H]1O
Temperature: 80 °C
Reaction time: 16 h
Yield: 133.7 %

Procedure:
A solution of (1R,2S)-1-[(5-bromo-3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol (1.48 g, 4.12 mmol) and 2,4-dichlorophenyl boronic acid (858 mg, 4.5 mmol) in benzene (41 mL) and 2M sodium carbonate (7 mL) was purged with nitrogen and treated with a single portion of bistriphenylphosphinepalladium(II)chloride (287 mg, 0.41 mmol). The resulting golden 2-phase solution was heated to 80° C. gradually darkening in color. After 16 hours, the reaction was cooled to room temperature, transferred to a separatory funnel, and washed with water (50 mL). The aqueous layer was extracted twice with ethyl acetate (75 mL) and the combined organics were washed once with brine (75 mL), dried over MgSO4, filtered, and concentrated to give 2.36 g of a brown syrup. This material was purified by biotage MPLC (90 g column, 20% ethyl acetate/heptane) to afford 1.25 g (71%) of the title compound as a tan solid. OAMS supporting ions at: ESI+ 428.0; HRMS (FAB) calcd for C23H23CL2N3O+H1 428.1296, found 428.1292.
Reaction SMILES: [CH:1](=[O:3])[CH3:2].[OH2:4]>>[CH2:2]([OH:4])[C@H:1]([C@H:2]([C@@H:1]([C@@H:2]([CH2:1][OH:3])[OH:4])[OH:3])[OH:4])[OH:3]
Reactant: O
Reactant: CC=O
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
There have been many attempts to fix aldehyde-generating volatile compounds in a variety of substrata. The most notable example is set out hereinbelow. The efficacy of such a fix is about 2% by weight. U.S. Pat. No. 3,314,803, issued to Dame et al. discloses a method for fixing acetaldehyde which includes first forming a solution of mannitol in water and preferably a super-saturated solution of mannitol, i.e., 25-45% mannitol solution. The super-saturated solution is formed by heating with agitation 2 to 10 parts by weight of mannitol with 10 parts by weight of water at 180°-212° F. until all of the mannitol is dissolved in water and no mannitol crystals remain in the solution. The mannitol solution is then cooled while acetaldehyde is added thereto, the acetaldehyde being continually refluxed and thereby condensed into mannitol solution until about 1 to 2 parts by weight of acetaldehyde are dissolved in a 10 parts by weight of water. The solution is then spray-dried with an initial acetaldehyde fix of approximately 4%-10% being obtained thereby. However, after one week exposure the level of acetaldehyde depleted to about 2.4% by weight of the total composition.
Reaction SMILES: [CH2:1]1[O:10][C:4]([CH2:6][CH2:7][CH2:8]Cl)([CH3:5])[O:3][CH2:2]1.[Br-:11].[Li+].C(N(C(C)C)CC)(C)C>O1CCCC1>[CH2:1]1[O:10][C:4]([CH2:6][CH2:7][CH2:8][Br:11])([CH3:5])[O:3][CH2:2]1
Reactant: CC1(CCCCl)OCCO1
Reactant: [Br-]
Agent: [Li+]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC1(CCCBr)OCCO1

Procedure:
4.0 Parts of 5-chloro-2-pentanone ethylene ketal is mixed with 9.0 parts of lithium bromide and 2.0 parts of diisopropylethylamine in 30 parts by volume of tetrahydrofuran which has been distilled from lithium aluminum hydride. The mixture is refluxed under nitrogen for 48 hours, cooled and poured into a mixture of ether and water for extraction. The ether layer is washed twice with water, then with 1 N hydrochloric acid and then twice again with water. The ether layer is then dried over sodium sulfate and evaporated under reduced pressure to give 5-bromo-2-pentanone ethylene ketal having the formula ##STR6##
Reaction SMILES: [C:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[N:6][CH:5]=1)(=[O:3])[CH3:2].C(O[CH:17](OCC)[N:18]([CH3:20])[CH3:19])C>>[CH3:17][N:18]([CH3:20])[CH:19]=[CH:2][C:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[N:6][CH:5]=1)=[O:3]
Reactant: CC(=O)c1cncc2ccccc12
Reactant: CCOC(OCC)N(C)C
Product: CN(C)C=CC(=O)c1cncc2ccccc12

Procedure:
2.0 g (11.6 mmol) of 4-acetylisoquinoline [J. Chem. Soc., Perkin Trans. 1, (7), 1503-8]are stirred in 50 ml of dimethyl formamide diethyl acetal for 1 hour at 110° C. The reaction mixture is concentrated under reduced pressure and the residue is chromatographed (methylene chloride:methanol=95:5), giving 3-dimethylamino-1-(4-isoquinolinyl)-2-propen-1-one; 1H-NMR (dimethyl sulfoxide): 2.9 (3H,s), 3.1 (3H,s), 5.52 (1H,d), 7.7-8.2 (m,5H), 8.6 (1H,s), 9.35 (1H,s).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[CH2:21]1[O:23][CH2:22]1>>[OH:23][CH2:21][CH2:22][N:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH3:1]
Reactant: CCCCCCCCCCCCCCCCCCNC
Reactant: C1CO1
Product: CCCCCCCCCCCCCCCCCCN(C)CCO
Temperature: 160 °C
Yield: 86.6 %

Procedure:
An autoclave provided with a stirrer, a thermometer, a pressure gauge and a pressure dropping funnel was charged with 250 g of N-methyloctadecylamine and heated to 160° C. Then 45 g of ethylene oxide was occasionally added dropwise thereto under a pressure of 0 to 6 kg/cm2G. Three hours were required for completing the addition. Next, the resulting mixture was aged, i.e., maintained, at 160° C. for 2 hours and then cooled. The reaction mixture was taken out and distilled to thereby give 250 g of N-(2-hydroxyethyl)-N-methyloctadecylamine. This product had a boiling point of 185° to 190° C./0.2 mmHg.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[CH:9][C:10]([C:19](=[N:22][OH:23])[CH2:20][CH3:21])=[N:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH3:26]I>C1COCC1>[CH3:26][O:23][N:22]=[C:19]([C:10]1[CH:9]=[CH:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:11]=1)[CH2:20][CH3:21]
Reactant: CI
Reactant: CCC(=NO)c1ccc(-c2ccccc2)c(-c2ccccc2)n1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(=NOC)c1ccc(-c2ccccc2)c(-c2ccccc2)n1

Procedure:
Following General Procedure Q, 1-(5,6-diphenyl-pyridin-2-yl)-propan-1-one oxime (Compound 81, 30 mg, 0.1 mmol), NaH (4.8 mg, 0.20 mmol) and MeI (140 mg, 0.99 mmol) in THF were reacted to obtain the title compound as an oil.
Reaction SMILES: [Si:1]([O:18][CH2:19][C:20]1[N:25]=[C:24]2[C:26]([C:29](OCC)=[O:30])=[N:27][O:28][C:23]2=[C:22]([Cl:34])[C:21]=1[N:35]1[CH2:40][C@H:39]([CH3:41])[O:38][C@H:37]([CH3:42])[CH2:36]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[F:44][C:45]1([F:49])[CH2:48][NH:47][CH2:46]1>>[Si:1]([O:18][CH2:19][C:20]1[N:25]=[C:24]2[C:26]([C:29]([N:47]3[CH2:48][C:45]([F:49])([F:44])[CH2:46]3)=[O:30])=[N:27][O:28][C:23]2=[C:22]([Cl:34])[C:21]=1[N:35]1[CH2:36][C@H:37]([CH3:42])[O:38][C@H:39]([CH3:41])[CH2:40]1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: FC1(F)CNC1
Reactant: CCOC(=O)c1noc2c(Cl)c(N3C[C@@H](C)O[C@@H](C)C3)c(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)nc12
Agent: Cl
Product: C[C@@H]1CN(c2c(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)nc3c(C(=O)N4CC(F)(F)C4)noc3c2Cl)C[C@H](C)O1

Procedure:
Starting material: ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-7-chloro-6-((2R,6S)-2,6-dimethylmorpholino)isoxazolo[4,5-b]pyridine-3-carboxylate (Intermediate 211) and 3,3-difluoroazetidine-HCl.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[N:5]=[N:6][C:7]2[C:12]([C:13]=1Cl)=[CH:11][CH:10]=[CH:9][C:8]=2[CH3:15].Cl.[NH2:17][C:18]1[C:19]([CH3:24])=[CH:20][CH:21]=[CH:22][CH:23]=1>O1CCOCC1>[CH3:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[N:17]1[C:13]2[C:12]3[CH:11]=[CH:10][CH:9]=[C:8]([CH3:15])[C:7]=3[N:6]=[N:5][C:4]=2[CH2:3][CH2:2]1
Reactant: Cc1cccc2c(Cl)c(CCCl)nnc12
Reactant: Cc1ccccc1N
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ccccc1N1CCc2nnc3c(C)cccc3c21

Procedure:
3-(2-Chloroethyl)-4-chloro-8-methylcinnoline (2.5 g, 0.01mol) and o-toluidine hydrochloride (1.4 g, 0.01 mol) in 1,4 dioxan (20 ml) were heated under reflux for 20 hours. The solvent was evaporated under reduced pressure to give an oil. The oil was partitioned between chloroform and dilute sodium carbonate solution and extracted further with chloroform (4×100 ml). The chloroform extracts were combined, dried over magnesium sulphate, filtered and evaporated to give an oil. The oil was purified by column chromatography using dichloromethane then chloroform as eluant. The solid obtained was recrystallized from diethyl ether/ dichloromethane to give the title compound, 0.6 g, m.p. 135-137°.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.[C:9]([C:11]1[C:12]([NH:17][C:18](=[O:23])[CH2:19][CH2:20][C:21]#[CH:22])=[N:13][CH:14]=[CH:15][CH:16]=1)#[N:10]>C(NCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:9]([C:11]1[C:12]([NH:17][C:18](=[O:23])[CH2:19][CH2:20][C:21]#[C:22][C:2]2[CH:3]=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=2)=[N:13][CH:14]=[CH:15][CH:16]=1)#[N:10]
Reactant: Cc1cccc(I)c1
Reactant: C#CCCC(=O)Nc1ncccc1C#N
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Product: Cc1cccc(C#CCCC(=O)Nc2ncccc2C#N)c1

Procedure:
Under an atmosphere of argon, bis(triphenylphosphine)palladium(II) chloride ([13965-03-2], 326 mg) and copper(I) iodide (44 mg) were added to a solution of 3-iodotoluene ([625-95-6], 506 mg, 2 mmol) and pent-4-ynoic acid (3-cyano-pyridin-2-yl)-amide (508 mg, 3 mmol) in diethylamine (15 ml). The mixture was kept at r.t. (3d). The volatiles were evaporated, and the residue was taken up in ethyl acetate. After washing (H2O) and drying (Na2SO4), the solvent was evaporated and 5-m-tolyl-pent-4-ynoic acid (3-cyano-pyridin-2-yl)-amide was isolated from the reaction mixture by column chromatography (silica gel, ethyl acetate/heptane). MS: m/e=290.1 [M+H+].