Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[H-].[Na+].Cl.Cl.[Cl:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20]([N:25]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]4[CH:33]=[N:34][N:35]([CH3:38])[C:36]=4[CH3:37])[CH2:27][CH2:26]3)=[N:21][CH:22]=[CH:23][N:24]=2)=[CH:15][CH:14]=1.[I-].[Na+].Cl>CN(C)C=O.C(#N)C.O>[ClH:11].[CH3:38][N:35]1[C:36]([CH3:37])=[C:32]([CH2:31][N:28]2[CH2:27][CH2:26][N:25]([C:20]3[C:19]([C:16]4[CH:15]=[CH:14][C:13]([CH2:12][N:3]5[CH:4]=[CH:5][N:6]=[C:2]5[CH3:1])=[CH:18][CH:17]=4)=[N:24][CH:23]=[CH:22][N:21]=3)[CH2:30][CH2:29]2)[CH:33]=[N:34]1
Reactant: Cc1c(CN2CCN(c3nccnc3-c3ccc(CCl)cc3)CC2)cnn1C
Reactant: Cc1ncc[nH]1
Agent: Cl
Agent: [H-]
Agent: [I-]
Solvent: CN(C)C=O
Solvent: CC#N
Solvent: O
Product: Cc1nccn1Cc1ccc(-c2nccnc2N2CCN(Cc3cnn(C)c3C)CC2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 51.8 %

Procedure:
Stir 2-methyl imidazole (164 mg, 2.00 mmol) in dry N,N-dimethylformamide (5 mL) under nitrogen. Add sodium hydride (60% weight dispersion in oil, 77 mg, 2.00 mmol), then stir for 1 hr. at room temperature. Add 3′-(4-chloromethyl-phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (233 mg, 0.50 mmol) at room temperature, followed by sodium iodide (75 mg, 0.50 mmol). Stir at room temperature for 20 hr. Quench reaction with water (20 mL), extract with DCM (3×10 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify by high pH reverse phase HPLC, and concentrate to give the free base. Dissolve the free base in acetonitrile and convert to the hydrochloride salt by adding 1 eq 2 M aq HCl solution. Add water and lyophilize to give the title compound as a light brown powder (124 mg, 52%). MS (ES): m/z=443 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.[CH2:14]([O:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)CCCC.[Cu]>[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]([NH:26][C:2]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])=[CH:27][CH:28]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: Nc1ccc(OCc2ccccc2)cc1
Reactant: COc1ccc(Br)c(C(=O)O)c1
Agent: [Cu]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCCCCO
Product: COc1ccc(Nc2ccc(OCc3ccccc3)cc2)c(C(=O)O)c1
Reaction time: 4.5 h
Yield: 70.1 %

Procedure:
A mixture of 231 g of 2-bromo-5-methoxybenzoic acid, 262 g of 4-benzyloxyaniline hydrochloride, 160 g of potassium carbonate and 2 g of activated copper powder in about 2100 ml of amyl alcohol was heated at reflux with stirring for 4.5 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in 6 liters of water. The solution was filtered and acidified with hydrochloric acid. The solid which formed was collected and recrystallized twice from benzene-cyclohexane to give 245 g of 2-(4-benzyloxyphenylamino)-5-methoxybenzoic acid, m.p. 167°-168° C.
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH:16]=O)=[CH:14][N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH:25]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:18]1([N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]([NH:10][C:11]2[S:12][C:13]([CH2:16][N:25]3[CH2:29][CH2:28][C:27](=[O:30])[NH:26]3)=[CH:14][N:15]=2)=[O:9])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1
Reactant: O=C1CCNN1
Reactant: O=Cc1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Product: O=C1CCN(Cc2cnc(NC(=O)N(C3CCCCC3)C3CCCCC3)s2)N1
Yield: 15.8 %

Procedure:
Prepared as described in general procedure (P) using 1,1-dicyclohexyl-3-(5-formyl-thiazol-2-yl)-urea (42 mg. 0.125 mmol), 3-pyrazolidinone hydrochloride (23 mg, 0.188 mmol) and sodium triacetoxyborohydride (40 mg, 0.188 mmol) to afford 8 mg (16%) of the desired product after purification.
Reaction SMILES: C(O)(=O)/C=C/C(O)=O.[NH2:9][C@H:10]([C:15]([O-:17])=[O:16])[CH2:11][C:12]([O-:14])=[O:13].[NH4+].[NH4+]>O>[NH2:9][C@H:10]([C:15]([OH:17])=[O:16])[CH2:11][C:12]([OH:14])=[O:13]
Reactant: N[C@@H](CC(=O)[O-])C(=O)[O-]
Agent: O=C(O)/C=C/C(=O)O
Agent: [NH4+]
Solvent: O
Product: N[C@@H](CC(=O)O)C(=O)O
Temperature: 20 °C
Reaction time: 1 h
Yield: 42.5 %

Procedure:
1.79 g of fumaric acid, with 25 g of water, were charged into a 100 ml Erlenmeyer flask. 24.8 g of the 37.27% w/w ammonium aspartate solution (0.0617 mol) of Example 1 were then added thereto. The liquid/solid mixture was then stirred for 1 h at a temperature of 20° C. After filtering, washing and drying, 3.49 g of L-aspartic acid were obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](Cl)=[O:8])([O-:3])=[O:2].[C:13]([C:17]1[CH:32]=[CH:31][C:20]([C:21]([NH:23][C:24]2[C:25]([NH2:30])=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:22])=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14]>>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([NH:30][C:25]1[C:24]([NH:23][C:21](=[O:22])[C:20]2[CH:31]=[CH:32][C:17]([C:13]([CH3:15])([CH3:14])[CH3:16])=[CH:18][CH:19]=2)=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:8])([O-:3])=[O:2]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: CC(C)(C)c1ccc(C(=O)Nc2ccccc2N)cc1
Product: CC(C)(C)c1ccc(C(=O)Nc2ccccc2NC(=O)c2cccc([N+](=O)[O-])c2)cc1
Yield: 56.8 %

Procedure:
Using the procedure described in Example 93, Part A, 3-nitrobenzoyl chloride (2.2 mmol) and N1-(4-tert-butylbenzoyl)-1,2-benzenediamine (1.8 mmol) yielded 427 mg (56%) of the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([F:10])=[C:6]([CH2:8][OH:9])[CH:7]=1.[F:11][C:12]([F:23])([F:22])[C:13]1[CH:14]=[CH:15][C:16]([CH2:19][CH2:20][NH2:21])=[N:17][CH:18]=1>>[F:10][C:5]1[CH:4]=[CH:3][C:2]([NH:21][CH2:20][CH2:19][C:16]2[CH:15]=[CH:14][C:13]([C:12]([F:23])([F:11])[F:22])=[CH:18][N:17]=2)=[CH:7][C:6]=1[CH2:8][OH:9]
Reactant: NCCc1ccc(C(F)(F)F)cn1
Reactant: OCc1cc(Br)ccc1F
Product: OCc1cc(NCCc2ccc(C(F)(F)F)cn2)ccc1F

Procedure:
In analogy to the procedure described for the synthesis example 71 (step 1), the title compound {2-fluoro-5-[2-(5-trifluoromethyl-pyridin-2-yl)-ethylamino]-phenyl}-methanol (MS m/e: 315.1 [M+H]+) was prepared from (5-bromo-2-fluoro-phenyl)-methanol instead of 6-bromo-2,3-dihydro-benzofuran and 2-(5-trifluoromethyl-pyridin-2-yl)-ethylamine instead of 2-(6-trifluoromethyl-pyridin-3-yl)-ethylamine.
Reaction SMILES: [BH3-]C#N.[Na+].[Cl:5][C:6]1[C:11]([N:12]=[C:13]([C@H:15]2[CH2:20][CH2:19][C@H:18]([CH3:21])[CH2:17][CH2:16]2)[CH3:14])=[C:10]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:9]=[C:8]([Cl:30])[N:7]=1.C(O)(=O)C>C(O)C>[Cl:5][C:6]1[C:11]([NH:12][CH:13]([C@H:15]2[CH2:16][CH2:17][C@H:18]([CH3:21])[CH2:19][CH2:20]2)[CH3:14])=[C:10]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:9]=[C:8]([Cl:30])[N:7]=1
Reactant: CC(=Nc1c(NC(=O)OC(C)(C)C)cc(Cl)nc1Cl)[C@H]1CC[C@H](C)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Product: CC(Nc1c(NC(=O)OC(C)(C)C)cc(Cl)nc1Cl)[C@H]1CC[C@H](C)CC1
Temperature: 50 °C

Procedure:
NaCNBH3 (100 g, 1.59 mol) was added to a mixture of tert-butyl (2,6-dichloro-3-((1-(trans-4-methylcyclohexyl)ethylidene)amino)pyridin-4-yl)carbamate (80 g, 0.2 mol) and acetic acid (60 mL) in ethanol (1.2 L). The mixture was heated to 50° C. for 4 h. TLC (petroleum ether/ethyl acetate=8:1) showed the reaction was complete. The reaction mixture was cooled down, poured into ice water, and then extracted with ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give crude tert-butyl (2,6-dichloro-3-((1-(trans-4-methylcyclohexyl)ethyl)amino)pyridin-4-yl)carbamate, which was used for the next step without further purification.
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[Sn](Cl)(Cl)(Cl)Cl.[Br:28][C:29]1[CH:42]=[CH:41][C:32]([CH2:33][C:34]2[O:35][C:36]([CH3:40])=[C:37]([CH3:39])[CH:38]=2)=[CH:31][CH:30]=1>CN(C)C=O>[Br:28][C:29]1[CH:42]=[CH:41][C:32]([CH2:33][C:34]2[O:35][C:36]([CH3:40])=[C:37]([CH3:39])[C:38]=2[C:9]([C:8]2[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH:7]=2)=[O:11])=[CH:31][CH:30]=1
Reactant: COc1ccc(C(=O)O)cc1C1CCCC1
Reactant: Cc1cc(Cc2ccc(Br)cc2)oc1C
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)c2c(Cc3ccc(Br)cc3)oc(C)c2C)cc1C1CCCC1
Yield: 78.5 %

Procedure:
The title compound was prepared according to the procedure in Example 5, step 2 using 3-cyclopentyl-p-anisic acid (2.04 g, 9.24 mmol, RN-59216-82-9), oxalyl chloride (0.887 mL, 10.2 mmol), N,N-dimethylformamide (2 drops), tin (IV) chloride (1.19 mL, 10.2 mmol) and 2-(4-bromo-benzyl)-4,5-dimethyl-furan (2.45 g, 9.24 mmol) in CH2C2. Purification on Biotage KP-Sil eluting with 4% EtOAc/pet. ether gave 3.39 g (78%) of the title compound. 1H NMR (DMSO-d6) δ1.38-1.47 (m, 2 H), 1.60-1.73 (m, 4 H), 1.79 (s, 3 H), 1.90-1.94 (m, 2 H), 2.18 (s, 3 H), 3.21 (quintet, 1 H) 3.82 (s, 2 H), 3.88 (s, 3 H), 7.02-7.08 (m, 3 H), 7.44 (d, 2 H), 7.55-7.61 (m , 2 H).
Reaction SMILES: [CH:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:29][O:30][C:31](=[O:45])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]([CH2:42][CH3:43])[CH2:40][CH3:41])=[C:34]([NH2:44])[CH:33]=1>CN(C=O)C.O.C(Cl)CCl>[CH3:29][O:30][C:31](=[O:45])[C:32]1[CH:37]=[CH:36][C:35]([NH:38][CH:39]([CH2:40][CH3:41])[CH2:42][CH3:43])=[C:34]([NH:44][C:7](=[O:9])[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[CH:33]=1
Reactant: O=C(O)CC1CCCC1
Reactant: CCC(CC)Nc1ccc(C(=O)OC)cc1N
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCC(CC)Nc1ccc(C(=O)OC)cc1NC(=O)CC1CCCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 72.8 %

Procedure:
To a solution of 16.41 g of cyclopentyl-acetic acid in 600 ml of dry DMF 17.30 g of HOBT, 24.54 g of EDC and 30 ml of DIPEA were added at 0° C. After 1 h 27.51 g of 3-amino-4-(1-ethyl-propylamino)-benzoic acid methyl ester and 30 ml of DIPEA were added and the reaction was stirred at rt for 16 h. The reaction was then poured into water and extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. The crude product was purified by crystallization from diisopropylether to yield 29.35 g (73%) of 3-(2-cyclopentyl-acetylamino)-4-(1-ethyl-propylamino)-benzoic acid methyl ester as an off-white solid.
Reaction SMILES: [Cl:1][C:2]([N:4]1[CH2:8][S:7](=[O:10])(=[O:9])[NH:6][C:5]1=[O:11])=[O:3].[CH3:12]C1(C)S[C@@H]2[C@H](NC([C@H](N)C3C=CC=CC=3)=O)C(=O)N2[C@H]1C(O)=O>>[Cl:1][C:2]([N:4]1[CH2:8][CH2:12][S:7](=[O:10])(=[O:9])[NH:6][C:5]1=[O:11])=[O:3]
Reactant: CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)O
Reactant: O=C(Cl)N1CS(=O)(=O)NC1=O
Product: O=C(Cl)N1CCS(=O)(=O)NC1=O

Procedure:
1-chlorocarbonyl-4-thia-imidazolidin-2-on-4,4-dioxide are reacted with 0.05 mol of ampicillin,
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[N+:20]([O-])=O)[C:5]([NH:7][CH2:8][C:9]([O:11]CC(Cl)(Cl)Cl)=[O:10])=[O:6].CC(O)=O>CCOC(C)=O.[Zn]>[NH2:20][C:19]1[CH:18]=[CH:17][C:4]([C:5]([NH:7][CH2:8][C:9]([OH:11])=[O:10])=[O:6])=[CH:3][C:2]=1[F:1]
Reactant: O=C(CNC(=O)c1ccc([N+](=O)[O-])c(F)c1)OCC(Cl)(Cl)Cl
Agent: [Zn]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Nc1ccc(C(=O)NCC(=O)O)cc1F
Temperature: 87.5 °C
Reaction time: 0.25 h
Yield: 80.1 %

Procedure:
A mixture of 2,2,2-trichloroethyl 2-(3-fluoro-4-nitrobenzamido)acetate (40 mg, 0.1 mmol), zinc dust (105 mg, 1.61 mmol) and AcOH (3 mL) was stirred at 85-90° C. for 15 min. The reaction mixture was attained to rt and diluted with EtOAc (30 mL). The solution was filtered through super cell and washed with EtOAc (2×5 mL). The residue obtained after evaporation of the solvent was chromatographed using chloroform:methanol (60:40) as eluents to give the product as an off-white color solid (17 mg, 75%), mp 198-200° C.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9](Cl)[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C-:15]#[N:16].[K+]>CN(C)C=O.O>[NH2:1][C:2]1[N:10]=[C:9]([C:15]#[N:16])[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: [C-]#N
Reactant: Nc1nc(Cl)c([N+](=O)[O-])cc1C(=O)O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1nc(N)c(C(=O)O)cc1[N+](=O)[O-]
Temperature: 90 °C
Yield: 84.4 %

Procedure:
The compound prepared in Example 238 (0.130 g) and potassium cyanide (0.195 g) were combined in N,N-dimethylformamide (3 mL) and water (0.5 mL) was added. The reaction mixture was heated at 90° C. for 3 hours. The mixture was diluted with water and extracted with ethyl acetate. The aqueous layer was cautiously acidified with 1N hydrochloric acid to pH 1 to 2. It was then extracted with ethyl acetate. These extracts were combined, washed with brine, dried over magnesium sulfate, filtered and concentrated to obtain the title compound (0.105 g) having the following physical data.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:39][O:40][C:41]1[C:42]2[N:55]=[C:54]([NH2:56])[S:53][C:43]=2[C:44]([N:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[N:45][CH:46]=1>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][C:5]([NH:56][C:54]1[S:53][C:43]2[C:44]([N:47]3[CH2:52][CH2:51][O:50][CH2:49][CH2:48]3)=[N:45][CH:46]=[C:41]([O:40][CH3:39])[C:42]=2[N:55]=1)=[O:7]
Reactant: COCCC(=O)O
Reactant: COc1cnc(N2CCOCC2)c2sc(N)nc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: COCCC(=O)Nc1nc2c(OC)cnc(N3CCOCC3)c2s1

Procedure:
From 3-methoxypropionic acid, HATU and N-methylmorpholine in THF, then treatment with 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine. ES-MS m/e (%): 353 (M+H+, 100).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[C:20]([S:23][CH2:24][CH:25]([CH3:29])[C:26](Cl)=[O:27])(=[O:22])[CH3:21]>C(Cl)Cl>[CH3:1][O:2][C:3]([CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]1[C:26](=[O:27])[CH:25]([CH3:29])[CH2:24][S:23][C:20](=[O:22])[CH3:21])=[O:4]
Reactant: COC(=O)C1Cc2ccccc2N1
Reactant: CC(=O)SCC(C)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: COC(=O)C1Cc2ccccc2N1C(=O)C(C)CSC(C)=O

Procedure:
To the stirred mixture of 5.0 g of indoline-2-carboxylic acid methyl ester [J. Am. Chem. Soc. 92, 2476 (1970)], 7.8 g of powdered potassium carbonate and 50 ml of methylene chloride, 5.1 g of 3-acetylthio-2-methylpropanoyl chloride (Belgium Pat. No. 868,532) in 20 ml of methylene chloride are added during 3 minutes at room temperature. After 2 hours the mixture is diluted with 100 ml of methylene chloride and washed with 100 ml of water, 100 ml of 1N hydrochloric acid and 100 ml of saturated aqueous sodium bicarbonate. The organic layer is dried and evaporated, to give the 1-(3-acetylthio-2-methylpropanoyl)-indoline-2-carboxylic acid methyl ester as an oil, showing in the IR-spectrum bands at 1710, 1690 and 1675 cm-1.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C:14]3[N:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:11][C:8]2=[N:9][CH:10]=1)(=[O:4])=[O:3].[H-].[Na+].[CH:22]1([CH2:28]Br)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:22]1([CH2:28][N:11]2[C:8]3=[N:9][CH:10]=[C:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH:6]=[C:7]3[CH:13]=[C:12]2[C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: BrCC1CCCCC1
Reactant: CS(=O)(=O)c1cnc2[nH]c(-c3ncccn3)cc2c1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1cnc2c(c1)cc(-c1ncccn1)n2CC1CCCCC1
Reaction time: 0.5 h
Yield: 53.8 %

Procedure:
To a suspension of 5-methanesulfonyl-2-(2-pyrimidinyl)-1H-pyrrolo[2,3-b]pyridine (150 mg) in N,N-dimethylformamide (5.5 ml), 60% sodium hydride (32.8 mg) was added at 0° C. under nitrogen atmosphere and the mixture was stirred at the same temperature for 30 minutes. Subsequently, to the mixture was added cyclohexylmethyl bromide (154 mg) at 0° C. and the mixture was stirred at 60° C. for 2 hours, followed by addition of cyclohexylmethyl bromide (77 mg) and stirring of the mixture at the same temperature for 1 hour. Further, to the mixture was added cyclohexylmethyl bromide (77 mg) and the mixture was stirred at 60° C. for 15 hours. Subsequently, the reaction solution was poured into a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The organic layer was washed with a saturated aqueous NaCl solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel preparative thin-layer chromatography (methanol:chloroform=1:20) and further recrystallized (chloroform/hexane) to obtain 109 mg of the desired product as a white needle-like crystal.
Reaction SMILES: N[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][C:3]=1[CH3:14].S([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[Cu](C#N)[C:28]#[N:29].[C-]#N.[K+]>Cl.O.C(OCC)(=O)C>[C:28]([C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][C:3]=1[CH3:14])#[N:29]
Reactant: N#C[Cu]C#N
Reactant: CCOC(=O)c1cc(C)c(N)c(C)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: O=S([O-])[O-]
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)c1cc(C)c(C#N)c(C)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
To a solution of ethyl 4-aminomesitylenate (6.6 g) in conc. hydrochloric acid (50 ml) was added a solution of sodium sulfite (2.6 g) in water (15 ml) at 0-5° C. over 30 min. This reaction mixture was stirred at 0° C. for 1 hr. To this reaction mixture was neutralized by adding sodium carbonate and then ethyl acetate (100 ml) was added. To a solution of copper cyanide (6.8 g) in water (100 ml) was added potassium cyanide (18 g) and the mixture was stirred at 0° C. for 30 min. The above-mentioned reaction mixture was added at 0-5° C. and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was extracted with ethyl acetate, washed with aqueous sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was recrystallized from ethyl acetate-hexane to give the title compound (5.5 g) as pale-brown crystals.
Reaction SMILES: S([O-])([O-])(=O)=O.[Ca+2].[CH3:7][CH:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1.[C:15](#[N:22])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].[OH-].[K+].OCC1OC1(C)CCC=C(C)C>CCCCCC>[CH3:7][CH:8]1[CH2:13][CH2:12][C:11](=[C:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:15]#[N:22])[CH2:10][CH2:9]1
Reactant: CCCCCCC#N
Reactant: CC1CCC(=O)CC1
Agent: CC(C)=CCCC1(C)OC1CO
Agent: O=S(=O)([O-])[O-]
Agent: [Ca+2]
Solvent: CCCCCC
Product: CCCCCC(C#N)=C1CCC(C)CC1
Temperature: 83 °C
Reaction time: 32 h

Procedure:
Into a 25 ml. flask, equipped with magnetic stirrer, heating mantle, thermometer, condensor and calcium sulfate drying tube, was charged 1.12 g. of 4-methyl cyclohexanone (0.01 M), 11.1 g. of heptanonitrile, and 0.66 g. of 85% KOH. The mixture was heated to reflux with stirring at about 83° C. for a total of 32 hours. After cooling, 30 ml. of hexane was added and the mixture washed seven times with 30 ml. of H2O, each washing being back-extracted twice with 30 ml. portions of hexane. The combined organic phase and hexane extracts were dried over anhydrous sodium sulfate and the solvent removed by rotary evaporation at about 15 mm. Hg to give 6.3 g. of crude oil. Gas chromatographic analysis (6' × 1/4" stainless steel column packed with 20% SE30 on chromasorb W, programmed at 135° to 220° C., 4°/minute, He flow ~60 ml./minute) showed two product peaks at RF 19.0 and 20.2 minutes, which were 6.9% in ratio to heptanonitrile. An IR spectrum of the product peaks, trapped as a group from the gas chromatograph, showed a nitrile band at 4.5 microns and an olefinic band at 6.25 microns. The product was evaluated by perfumers as having a jasminic nitrile type odor with a strong, nerol oxide note.
Reaction SMILES: CS(O[CH2:6][C:7]1[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:14]=2)[CH:10]=[C:9]([Cl:24])[CH:8]=1)(=O)=O.[C-:25]#[N:26].[Na+]>CN(C)C=O.C(OCC)C>[Cl:24][C:9]1[CH:8]=[C:7]([CH2:6][C:25]#[N:26])[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:14]=2)[CH:10]=1
Reactant: [C-]#N
Reactant: C[Si](C)(C)CCOCn1cc2cc(Cl)cc(COS(C)(=O)=O)c2n1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C[Si](C)(C)CCOCn1cc2cc(Cl)cc(CC#N)c2n1
Reaction time: 0.5 h

Procedure:
To a solution of (5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methyl methanesulfonate (3.25 g, 8.3 mmol) in dimethylformamide (10 mL) at room temperature was added sodium cyanide (0.815 g, 16.6 mmol). The reaction was placed in a 60° C. oil bath and allowed to stir for 30 min. The reaction was cooled, diluted with diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated to give 2.33 g (87%). 1H-NMR (CDCl3, 500 MHz) δ 8.07 (s, 1H), 7.62 (d, J=1.2 Hz, 1H), 7.32 (d, J=1.2 Hz, 1H), 5.68 (s, 2H), 4.09 (s, 2H), 3.62 (t, J=8.2 Hz, 2H), 0.93 (t, J=7.9 Hz, 2H), -0.04 (s, 9H), 13C NMR (126 MHz, CDCl3) δ ppm 145.7, 127.7, 126.4, 123.2, 122.4, 121.8, 119.5, 117.0, 82.1, 67.9, 19.4, 17.9, −1.4.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH2:9]([O:16][C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]=1[CH:27]([OH:33])[C:28](=[NH:32])[O:29]CC)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[O:34]1CCC[CH2:35]1>C1(C)C=CC=CC=1>[CH2:9]([O:16][C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]=1[CH:27]1[O:33][C:35](=[O:34])[NH:29][C:28]1=[O:32])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: C1CCOC1
Reactant: CCOC(=N)C(O)c1c(OCc2ccccc2)ccc2ccccc12
Agent: Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C1NC(=O)C(c2c(OCc3ccccc3)ccc3ccccc23)O1

Procedure:
By the procedure of Example 27, except that 2.1 equivalents rather than 3.2 equivalents of triethylamine were employed, ethyl 1-(2-benzyloxy-1-naphthyl)-1-hydroxymethanecarboximidate hydrochloride (4.0 g., 0.011 mole) in 180 ml. of tetrahydrofuran was converted to toluene recrystallized 5-(2-benzyloxy-1-naphthyl)oxazolidine-2,4-dione (1.61 g., m.p. 197°-199.5° C.).
Reaction SMILES: [OH:1][C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.I[CH2:13][CH2:14][CH3:15].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[CH2:13]([O:1][C:2]1[C:3]([C:8]([O:10][CH3:11])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1)[CH2:14][CH3:15]
Reactant: COC(=O)c1ncccc1O
Reactant: CCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCOc1cccnc1C(=O)OC
Temperature: 80 °C
Reaction time: 3 h
Yield: 69.5 %

Procedure:
To a solution of methyl 3-hydroxypicolinate (0.472 g, 3.08 mmol) in N,N-dimethylformamide (6 ml) were added 1-iodopropane (0.33 ml, 3.38 mmol) and potassium carbonate (0.519 g, 3.76 mmol), and the mixture was stirred at 80° C. for 3 hr. Ethyl acetate was added to the reaction mixture, the mixture was washed with water, and the organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate) to give methyl 3-propyloxypicolinate (0.418 g, 2.14 mmol, yield 69%). This was dissolved in methanol (5 ml), 1N-aqueous sodium hydroxide m solution (5 ml) was added at room temperature, and the mixture was stirred at 60° C. for 3.5 hr. The reaction mixture was concentrated under reduced pressure and neutralized with 5%-aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate, and the solvent was evaporated under reduced pressure to give a carboxylic acid compound 3-propyloxypicolinic acid (0.248 g, 1.37 mmol, yield 64%).