Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15]([C:18]3[CH:19]=[C:20]([N:24]4[CH2:29][CH2:28][CH:27]([NH:30]C(=O)OC(C)(C)C)[CH2:26][CH2:25]4)[CH:21]=[N:22][CH:23]=3)=[CH:16][NH:17][C:12]2=[CH:11][CH:10]=1.Cl.CC(O)C>CO.CO.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15]([C:18]3[CH:19]=[C:20]([N:24]4[CH2:25][CH2:26][CH:27]([NH2:30])[CH2:28][CH2:29]4)[CH:21]=[N:22][CH:23]=3)=[CH:16][NH:17][C:12]2=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)NC1CCN(c2cncc(-c3c[nH]c4ccc(-c5c(F)cccc5F)nc34)c2)CC1
Agent: Cl
Solvent: CO
Solvent: ClCCl
Solvent: CC(C)O
Product: NC1CCN(c2cncc(-c3c[nH]c4ccc(-c5c(F)cccc5F)nc34)c2)CC1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
A solution of tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (79 mg, 0.120 mmol, 88% pure) in THF (2 mL) was treated with NaOH 5M (0.048 mL, 0.239 mmol). The reaction mixture was heated to reflux (bath temperature 80° C.). After 1 h, NaOH 5M (0.45 mL, 0.96 mmol, 8.0 equiv) was further added. After 23 h, the solution was cooled to 23° C., concentrated in vacuo and purified by silica gel chromatography (eluent: 1-7% MeOH/DCM), affording tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (31 mg, 51%). MS (ESI, pos. ion) m/z: 506.2 (M+1). A solution of tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (31 mg, 0.061 mmol) in MeOH (0.5 mL) was treated with HCl, 5-6n in IPA (0.123 mL, 0.613 mmol). The reaction was heated to 50° C. under N2. After 2 h, the reaction was cooled to 23° C. and the product (as HCl salt) was free-based using a Silicycle Si-propylsulfonic acid ion exchange column (catalog # R51230B). The compound was slurried in MeOH/DCM and added to a pad of the resin (wetted and flushed with 10 mL MeOH). It was flushed with MeOH (50 mL), and then the product was “released” using 2.0 M NH3 in MeOH solution (50 ml). The final filtrate was concentrated, affording 1-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-amine MS (ESI, pos. ion) m/z: 406.3 (M+1).
Reaction SMILES: CO[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:23]([NH:24][CH:25]([CH3:27])[CH3:26])=[CH:22][CH:21]=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[O:11])=[N:6][CH:5]=1.[CH:29]1([NH2:32])[CH2:31][CH2:30]1>>[CH:29]1([NH:32][C:3]([C:4]2[CH:9]=[CH:8][C:7]([C:10]([N:12]3[CH2:13][CH2:14][N:15]([C:18]4[C:23]([NH:24][CH:25]([CH3:27])[CH3:26])=[CH:22][CH:21]=[CH:20][N:19]=4)[CH2:16][CH2:17]3)=[O:11])=[N:6][CH:5]=2)=[O:28])[CH2:31][CH2:30]1
Reactant: NC1CC1
Reactant: COC(=O)c1ccc(C(=O)N2CCN(c3ncccc3NC(C)C)CC2)nc1
Product: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)NC3CC3)cn2)CC1
Yield: 77 %

Procedure:
By the same procedure as described in the example 25, the synthesis was carried out starting with 6-[1-[3-(isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]nicotinic acid methyl ester and using cyclopropylamine. And then, the product was recrystallized with isopropanol and petroleum ether to give a desired compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[O:5][CH2:6][C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](OC(C)(C)C)=O.ClC1[N:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:24]=1[C:25]([NH:27][C:28]1([C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29]1)=[O:26]>>[Cl:45][C:42]1[CH:43]=[N:44][C:12]([N:8]2[CH2:9][CH2:10][CH2:11][C@H:7]2[CH2:6][O:5][C:4]2[CH:19]=[CH:20][CH:21]=[C:2]([F:1])[CH:3]=2)=[C:24]([CH:41]=1)[C:25]([NH:27][C:28]1([C:31]2[CH:32]=[CH:33][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:39][CH:40]=2)[CH2:30][CH2:29]1)=[O:26]
Reactant: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3Cl)CC2)cc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1COc1cccc(F)c1
Product: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3N3CCC[C@H]3COc3cccc(F)c3)CC2)cc1
Yield: 100.5 %

Procedure:
The title compound (D202) (89 mg) was prepared according to the experimental procedure described in Description 160 starting from (S)-tert-butyl 2-((3-fluorophenoxy)methyl)pyrrolidine-1-carboxylate (D44) (100 mg, 0.338 mmol) and reacting in the second step with methyl 4-(1-(2,5-dichloronicotinamido)cyclopropyl)benzoate (D97) (61.8 mg, 0.169 mmol).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:5][C:6]([N+:13]([O-])=O)=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].[H][H]>CCOC(C)=O.[Pd]>[NH2:13][C:6]1[CH:5]=[C:4]([O:16][CH2:17][CH2:18][O:19][CH3:20])[C:3]([O:2][CH3:1])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9]
Reactant: COCCOc1cc([N+](=O)[O-])c(C(=O)OC)cc1OC
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COCCOc1cc(N)c(C(=O)OC)cc1OC
Yield: 94.4 %

Procedure:
According to the procedure described in Example 6A Step 3, a mixture of methyl 5-methoxy-4-(2-methoxyethoxy)-2-nitrobenzoate (3.19 g, 11.2 mmol) and Pd/C (10%, 0.3 g) in EtOAc (150 mL) was stirred under 1 atmosphere of hydrogen at room temperature for 6 hours, to afford methyl 2-amino-5-methoxy-4-(2-methoxyethoxy)benzoate as a solid (2.699 g, 95%). 1H NMR (300 MHz, CDCl3) δ 7.30 (s, 1H), 6.17 (s, 1H), 5.55 (br, 2H), 4.14 (t, 2H), 3.85 (s, 3H), 3.80 (s, 3H), 3.79 (t. 2H), 3.44 (s, 3H); LC-MS (ESI) m/z 256 (M+H)+.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][C:17]3=[CH:19][N:20]=[C:21]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[N:16]3[C:15]2=[O:31])[CH2:10][CH2:9]1)C1C=CC=CC=1>CO.[C].[Pd]>[Si:24]([O:23][CH2:22][C:21]1[N:16]2[C:15](=[O:31])[N:14]([CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH2:18][C:17]2=[CH:19][N:20]=1)([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:26])[CH3:25]
Reactant: CC(C)(C)[Si](C)(C)OCc1ncc2n1C(=O)N(C1CCN(Cc3ccccc3)CC1)C2
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)[Si](C)(C)OCc1ncc2n1C(=O)N(C1CCNCC1)C2
Yield: 111.7 %

Procedure:
2-(1-Benzyl-4-piperidinyl)-5-(((tert-butyldimethylsilyl)oxy)methyl)-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one (0.18 g) obtained in Example 83h) and 10% palladium carbon (36 mg) were suspended in methanol (3 ml), and mixed under hydrogen atmosphere at room temperature for 18 hours. The reaction solution was filtered using Celite, and the filtrate was concentrated under reduced pressure to obtain the title compound as a colorless solid (0.16 g, quantitative).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C:9]1[C:10]([CH3:31])=[C:11]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22]([O:29][CH3:30])[CH:21]=2)=[O:19])[N:12]2[C:17]=1[CH:16]=[CH:15][CH:14]=[CH:13]2>ClCCl>[CH3:30][O:29][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][C:23]=1[N+:26]([O-:28])=[O:27])[C:18]([C:11]1[N:12]2[C:17]([CH:16]=[CH:15][CH:14]=[CH:13]2)=[C:9]([NH:8][C:1](=[O:3])[CH3:2])[C:10]=1[CH3:31])=[O:19]
Reactant: COc1cc(C(=O)c2c(C)c(N)c3ccccn23)ccc1[N+](=O)[O-]
Reactant: CC(=O)OC(C)=O
Solvent: ClCCl
Product: COc1cc(C(=O)c2c(C)c(NC(C)=O)c3ccccn23)ccc1[N+](=O)[O-]

Procedure:
1.20 ml (12.60 mmol) of acetic anhydride are added to 410 mg (1.26 mmol) of (1-amino-2-methylindolizin-3-yl)(3-methoxy-4-nitrophenyl)methanone dissolved in 10 ml of dichloromethane.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([CH:8]=O)=[N:6][CH:7]=1.[CH3:11][O:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[CH2:21][NH2:22].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([CH2:8][NH:22][CH2:21][C:14]2[CH:15]=[CH:16][C:17]([O:19][CH3:20])=[CH:18][C:13]=2[O:12][CH3:11])=[N:6][CH:7]=1
Reactant: Cc1cc(Br)cnc1C=O
Reactant: COc1ccc(CN)c(OC)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: COc1ccc(CNCc2ncc(Br)cc2C)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To the solution of 5-bromo-3-methylpicolinaldehyde 81-1 (1.0 g, 5 mmol), (2,4-dimethoxyphenyl)methanamine 81-2 (0.83 g, 5 mmol), acetic acid (0.9 g, 15 mmol) in DMF (10 mL) was added Na(OAc)3BH (2.46 g, 15 mmol) at room temperature. The reaction was stirred at room temperature overnight. The reaction was diluted with ethyl acetate and washed with aqueous Na2CO3 and brine. The organic phase was dried to give crude 1-(5-bromo-3-methylpyridin-2-yl)-N-(2,4-dimethoxybenzyl)methanamine 81-3. MS m/z 351.2 (M+1).
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([Br:13])[CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.[C-:14]#[N:15].[K+]>CN(C=O)C.O>[Br:13][C:11]1[CH:12]=[C:3]([CH2:2][C:14]#[N:15])[CH:4]=[C:5]2[C:10]=1[N:9]=[CH:8][CH:7]=[CH:6]2
Reactant: BrCc1cc(Br)c2ncccc2c1
Reactant: [C-]#N
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: N#CCc1cc(Br)c2ncccc2c1
Temperature: 100 °C

Procedure:
To a solution 6-bromomethyl-8-bromoquinoline (described in International Patent Publication WO 94/22852) (1.0 eq) in DMF:H2O (2:1, 0.66M) was added potassium cyanide (2.5 eq). After heating at 100° C. for 1 h, the resulting mixture was quenched with H2O and extracted with EtOAc (2 x). The combined organic extracts were washed with water (3×), brine, dried over MgSO4, filtered and concentrated. Flash chromatography (Hex:EtOAc, 3:1) yielded the desired compound as a white solid.
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:11]([Cl:12])=[C:10]([O:13][CH3:14])[CH:9]=[CH:8][N:7]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[Cl:12][C:11]1[C:6]([CH2:5][OH:4])=[N:7][CH:8]=[CH:9][C:10]=1[O:13][CH3:14]
Reactant: COc1ccnc(COC(C)=O)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COc1ccnc(CO)c1Cl
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 95.2 %

Procedure:
The above (3-chloro-4-methoxypyridin-2-yl)methyl acetate (570 mg) was dissolved in methanol (13 mL), and potassium carbonate (731 mg) was then added to the solution. The resulting mixture was stirred at 50° C. for 30 minutes. Thereafter, methanol was distilled away under reduced pressure, and water was then added to the residue, followed by extraction with chloroform three times. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was then distilled away under reduced pressure, so as to obtain the title compound (437 mg) as an oily substance.
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:12][C:13]1([F:31])[CH2:18][CH2:17][C:16]([CH2:29][NH2:30])([C:19]2[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=2)[CH2:15][CH2:14]1>>[Cl:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:30][CH2:29][C:16]1([C:19]2[CH:20]=[N:21][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:23][CH:24]=2)[CH2:17][CH2:18][C:13]([F:12])([F:31])[CH2:14][CH2:15]1)=[O:6]
Reactant: Cc1cccc(C(=O)O)c1Cl
Reactant: NCC1(c2ccc(C(F)(F)F)nc2)CCC(F)(F)CC1
Product: Cc1cccc(C(=O)NCC2(c3ccc(C(F)(F)F)nc3)CCC(F)(F)CC2)c1Cl

Procedure:
From 2-chloro-3-methylbenzoic acid and C-[4,4-difluoro-1-(6-trifluoromethyl-pyridin-3-yl)-cyclohexyl]-methylamine. LCMS (MH+): m/z=447.1, tR (minutes, Method D)=0.80
Reaction SMILES: [CH3:1][C:2]1[C@@H:19](O)[CH2:18][C@:14]2(O)[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4](OC(C)=O)[C:5]([C@@:7]1([CH3:38])[C@H:12]([C@@H:13]2OC(C2C=CC=CC=2)=O)[C@:11]2(OC(C)=O)[CH2:31]O[C@@H:10]2[CH2:9][C@@H:8]1O)=O.C(=O)=O.C(#N)C.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>O1CCCC1>[CH3:31][C@H:11]1[C@H:12]2[CH2:13][C@H:14]3[C:15]([CH3:16])([CH3:17])[C@@H:3]([CH2:4][CH2:5][C@:7]2([CH3:38])[CH2:8][CH2:9][CH2:10]1)[C@H:2]([CH3:1])[CH2:19][CH2:18]3
Reactant: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](O)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=C=O
Agent: [Na+]
Solvent: CC#N
Solvent: C1CCOC1
Product: C[C@@H]1CCC[C@@]2(C)CC[C@H]3[C@H](C)CC[C@@H](C[C@H]12)C3(C)C
Reaction time: 0.5 h
Yield: 190.1 %

Procedure:
Coupling reaction: the C-7 triethylsilylprotected baccatin III (0.048 g; 0.0685 mmol) and the triethylsily-isopropyl-β-lactam (3) (0.043 g; 0.0978 mmol; 1.4 eq.) were dissolved in 3.6 ml dry tetrahydrofuran. The solution was cooled to a temperature in the range −45° C. to −50° C. (dry ice-acetonitrile bath) under nitrogen. The base sodium bistrimethylsilylamide (NaHMDS) (1.0 M) solution in tetrahydrofuran; 0.175 ml; 175 mmol; 2.6 eq) was added in one portion at a temperature of −45° C. and the reaction was stirred for 30 min at this temperature. The solution became yellow and was quenched at 30 min with an ammonium chloride saturated solution. The work up consisted of quenching the reaction with saturated ammonium chloride, extracting with ethyl acetate, washing the organic phase with brine and drying the organic layer with magnesium sulphate. After filtration the solvent was evaporated and flash chromatography of the residue with 20% ethyl acetate/hexane in a 6″ chromatography column; 36 mg of the coupled protected taxane (5) was obtained with 14 mg of starting material recovered (4, uncoupled protected baccatin III).
Reaction SMILES: [C:1]([C:3]1[CH:30]=[C:29]([N+:31]([O-])=O)[CH:28]=[CH:27][C:4]=1[O:5][C:6]1[CH:7]=[CH:8][C:9]([F:26])=[C:10]([NH:12][C:13](=[O:25])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH:11]=1)#[N:2].O1CCCC1>C(O)C.[C].[Pd]>[NH2:31][C:29]1[CH:28]=[CH:27][C:4]([O:5][C:6]2[CH:7]=[CH:8][C:9]([F:26])=[C:10]([NH:12][C:13](=[O:25])[CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:23])[F:24])[CH:16]=3)[CH:11]=2)=[C:3]([C:1]#[N:2])[CH:30]=1
Reactant: N#Cc1cc([N+](=O)[O-])ccc1Oc1ccc(F)c(NC(=O)Cc2cccc(C(F)(F)F)c2)c1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: N#Cc1cc(N)ccc1Oc1ccc(F)c(NC(=O)Cc2cccc(C(F)(F)F)c2)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 92.1 %

Procedure:
To a solution of N-[5-(2-cyano-4-nitrophenoxy)-2-fluorophenyl]-2-[3-(trifluoromethyl)phenyl]acetamide (1.36 g, 2.96 mmol) in ethanol (25 mL)/tetrahydrofuran (10 mL) was added 10% palladium-carbon (160 mg), and the mixture was stirred at room temperature for 5 hr under a hydrogen atmosphere (1 atm). Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=30/70→100/0), and the fraction containing the object product was concentrated under reduced pressure to give the title compound (1.17 g, 92%) as a beige amorphous form.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:12]2=[N:13][CH:14]=[CH:15][C:16]([CH2:17][NH:18][C:19]3([C:24](O)=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:11]2[C:10]([C:27]([O:29][CH3:30])=[O:28])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=N[C:41]2[CH:42]=[CH:43][CH:44]=[N:45][C:40]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(N)CCCC1.CN1CCOCC1>C1COCC1>[CH:40]1([NH:45][C:24]([C:19]2([NH:18][CH2:17][C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:9]=[C:10]([C:27]([O:29][CH3:30])=[O:28])[C:11]=34)[CH2:20][CH2:21][CH2:22][CH2:23]2)=[O:25])[CH2:41][CH2:42][CH2:43][CH2:44]1
Reactant: COC(=O)c1cn(C(=O)OC(C)(C)C)c2nccc(CNC3(C(=O)O)CCCC3)c12
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CCCC1
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: COC(=O)c1cn(C(=O)OC(C)(C)C)c2nccc(CNC3(C(=O)NC4CCCC4)CCCC3)c12
Temperature: 43 °C
Reaction time: 36 h

Procedure:
To 1-((1-(tert-butoxycarbonyl)-3-(methoxycarbonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methylamino)cyclopentanecarboxylic acid was added THF (2 mL), HATU (94 mg, 0.246 mmol), cyclopentanamine (70.0 mg, 0.822 mmol) and 4-methylmorpholine (83 mg, 0.822 mmol). The suspension was stirred at 43° C. for 36 h to afford the title compound, which was used in the next step without further purification. [M+H] calc'd for C26H36N4O5, 485; found, 485.4.
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]=[C:7]([O:16][CH3:17])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([F:15])=[CH:10][CH:9]=2)=[O:4].[OH-].[Na+]>CO>[F:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[C:7]([O:16][CH3:17])=[N:6][C:5]([C:3]([OH:4])=[O:2])=[CH:14]2
Reactant: COC(=O)c1cc2cc(F)ccc2c(OC)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1nc(C(=O)O)cc2cc(F)ccc12

Procedure:
690 mg (2.93 mmol) 6-fluoro-1-methoxy-isoquinoline-3-carboxylic acid methyl ester was dissolved in 20 mL MeOH and treated with 3.75 mL 4 M aqueous NaOH solution at RT for 3 h. The solvent was removed by distillation, the residue taken up in water and acidified with 4 M aqueous hydrochlorid acid. The precipitate was filtered off, washed with water and purified by HPLC.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](=[O:14])[CH2:12][CH3:13])=[CH:10][C:5]=2[O:4][C:3]1=[O:15].[CH3:16]N(CN(C)C)C.C(OC(=O)C)(=O)C>>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](=[O:14])[C:12](=[CH2:16])[CH3:13])=[CH:10][C:5]=2[O:4][C:3]1=[O:15]
Reactant: CN(C)CN(C)C
Reactant: CCC(=O)c1ccc2c(c1)oc(=O)n2C
Solvent: CC(=O)OC(C)=O
Product: C=C(C)C(=O)c1ccc2c(c1)oc(=O)n2C
Temperature: 100 °C
Reaction time: 1 h

Procedure:
0.01 mole of 3-methyl-6-propionylbenzoxazolinone and 0.04 mole of bis(dimethylamino)methane are introduced into a 150-cm3 ground-necked flask equipped with a reflux condenser and a magnetic stirrer. 15 cm3 of acetic anhydride are added dropwise and the mixture is heated to 100° C. for 5 hours. After being cooled, the reaction mixture is poured into 5 volumes of ice-cold water. The mixture is acidified and stirred for one hour, and the product is drained, washed with water to neutrality, dried and recrystallized in hexane.
Reaction SMILES: [CH2:1]([CH2:11][C:12](=O)[CH3:13])/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])\[CH3:4].C([N:17](CC)[C:18](=[O:24])[CH2:19]P(O)(O)=O)C.[H-].[Na+].O>C(COC)OC>[CH3:13]/[C:12](/[CH2:11][CH2:1]/[CH:2]=[C:3](\[CH3:4])/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])=[CH:19]\[C:18]([NH2:17])=[O:24]
Reactant: CC(=O)CC/C=C(\C)CCC=C(C)C
Reactant: CCN(CC)C(=O)CP(=O)(O)O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/C(N)=O
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
A solution of 5 g of E-geranylacetone in 90 ml of dimethoxyethane is treated at -20° with 25.1 g of phosphonoacetamide diethyl ester and 1.86 g of 50% sodium hydride dispersion in mineral oil. The reaction mixture is stirred at room temperature for 3.5 hours under argon. After the addition of water the mixture is extracted with ethyl acetate. The organic phase is dried and freed from solvent. Crystallization of the (2E/Z,6E)-3,7,11-trimethyl-2,6,10-dodecatrienamide (4:1 2E/Z mixture), which remains behind as the residue, from hexane gives white crystals, m.p. 51°-52.5°. This material is recrystallized a further twice from hexane, there being obtained pure (E,E)-3,7,11-trimethyl-2,6,10-dodecatrienamide as a white crystalline material of m.p. 53°-53.5°.