Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=2)[C:6](=[C:18](OCC)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]1=[O:28])(=O)C.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:32][CH:31]=1>>[C:40]([O:39][C:37]([CH2:36][C:33]1[CH:34]=[CH:35][C:30]([NH:29]/[C:18](=[C:6]2\[C:5](=[O:28])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:11]=3)/[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:31][CH:32]=1)=[O:38])([CH3:43])([CH3:41])[CH3:42]
Reactant: CCOC(=O)c1ccc2c(c1)N(C(C)=O)C(=O)C2=C(OCC)c1ccccc1
Reactant: CC(C)(C)OC(=O)Cc1ccc(N)cc1
Product: CCOC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(CC(=O)OC(C)(C)C)cc1)c1ccccc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and tert.butyl 4-aminophenylacetate Rf value: 0.5 (aluminium oxide, ethyl acetate) C30H30N2O5
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11]Cl)(=[O:10])=[O:9])=[CH:6][CH:7]=1.[CH2:13]([C:15]([CH2:17][CH3:18])=[CH2:16])[CH3:14].[Br-].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>C(#N)C>[CH2:13]([C:15]1([CH2:17][CH3:18])[CH2:16][N:11]1[S:8]([C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=1)(=[O:10])=[O:9])[CH3:14]
Reactant: C=C(CC)CC
Reactant: Cc1ccc(S(=O)(=O)NCl)cc1
Agent: C[N+](C)(C)c1ccccc1
Agent: [Br-]
Solvent: CC#N
Product: CCC1(CC)CN1S(=O)(=O)c1ccc(C)cc1
Yield: 40.5 %

Procedure:
Chloramine-T (10 g, 43.9 mmol) was suspended in acetonitrile (146 mL) at room temperature under nitrogen. To this suspension was added 2-ethylbut-1-ene (5.55 g, 65.9 mmol) followed by phenyltrimethylammonium tribromide (1.65 g, 4.39 mmol) in two roughly equal portions. After three days the reaction mixture was concentrated to half volume and then filtered through a sintered glass funnel. The filtrate was concentrated to half volume again which caused further precipitation. This mixture was filtered and the filtrate was partitioned between ethyl acetate and water. The organic phase was dried with MgSO4, filtered and concentrated. The crude material was purified by column chromatography using a Biotage 65i column eluting with (0-100% EtOAc/hexane) to give 2,2-diethyl-1-[(4-methylphenyl)sulfonyl]-aziridine as a colorless solid (4.5 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:18][NH:17][C:16](=[O:19])[C:15]=2[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH2:23])=[N-]>CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:18][N:17]=[C:16]([O:19][CH3:23])[C:15]=2[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1c(C2CCN(C(=O)OC(C)(C)C)CC2)[nH][nH]c1=O
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Product: COc1n[nH]c(C2CCN(C(=O)OC(C)(C)C)CC2)c1C

Procedure:
A suspension of 1-tert-butoxycarbonyl-4-(4-methyl-(1H)-pyrazol-3-one-5-yl)piperidine (from Step C) in 12.5 mL (9.9 mmol) of 0.8 M diazomethane in Et2O was allowed to stand (occasional swirling) until all solids were in solution. Excess diazomethane was quenched with HOAc. The reaction was partitioned between 1 N NaHCO3 and Et2O. After separating phases, the organic layer was dried over MgSO4 and concentrated. The residue was purified by flash chromatography using 19:1 v/v hexanes/acetone, 9:1 v/v hexanes/acetone and 4:1 v/v hexanes/acetone as the gradient to afford the title compound as a yellow oil: RF: 0.18 (4:1 v/v hexanes/acetone); 1H-NMR (500 MHz) δ 1.48 (s, 9H), 1.57–1.65 (m, 2H), 1.82–1.85 (m, 2H), 1.89 (s, 3H), 2.70–2.79 (m, 3H), 3.91 (s, 3H), 4.24 (m, 2H)-; 13C-NMR (125 MHz) δ 55.7 (O—CH3).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=[O:12])[CH:6]3[CH2:13][O:14][CH2:15][CH2:16][N:5]3[C:4]=2[N:3]=1.[CH3:17][C:18]([CH3:21])([O-])[CH3:19].[Na+].BrCC1CC1.O>CS(C)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:17][CH:18]3[CH2:21][CH2:19]3)[C:7](=[O:12])[CH:6]3[CH2:13][O:14][CH2:15][CH2:16][N:5]3[C:4]=2[N:3]=1
Reactant: O=C1Nc2cnc(Cl)nc2N2CCOCC12
Reactant: CC(C)(C)[O-]
Agent: BrCC1CC1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: O=C1C2COCCN2c2nc(Cl)ncc2N1CC1CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 97.1 %

Procedure:
To a mixture of 2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (3 g, 12.47 mmol) in DMSO (10 mL) cooled in an ice water bath was added sodium tert-butoxide (1.32 g, 13.7 mmol). After 15 minutes stirring, the mixture was allowed to warm up to room temperature and stirred for 45 minutes. Then (bromomethyl)cyclopropane (1.27 mL, 13 mmol) was added dropwise in 12 minutes and the resulting mixture stirred at room temperature for 15 hours. Water was added and the resulting yellow precipitate was collected by vacuum filtration and washed repeatedly with water. The solid was subjected to vacuum for 4 hours to give 2-chloro-5-(cyclopropylmethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one as a yellow solid (3.57 g, 97%). MS [M+H] found 295.2.
Reaction SMILES: NC1(C2C=CC(C3C(=O)C4C(=CC([C:23]([NH2:25])=[O:24])=CC=4)OC=3C3C=CC=CC=3)=CC=2)CCC1.[C:32]([O:36][C:37](=[O:69])[NH:38][C:39]1([C:43]2[CH:48]=[CH:47][C:46]([C:49]3[C:58](=[O:59])[C:57]4[C:52](=[CH:53][C:54](Br)=[C:55]([O:60][CH3:61])[CH:56]=4)[O:51][C:50]=3[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[CH:45][CH:44]=2)[CH2:42][CH2:41][CH2:40]1)([CH3:35])([CH3:34])[CH3:33]>>[C:32]([O:36][C:37](=[O:69])[NH:38][C:39]1([C:43]2[CH:48]=[CH:47][C:46]([C:49]3[C:58](=[O:59])[C:57]4[C:52](=[CH:53][C:54]([C:23](=[O:24])[NH2:25])=[C:55]([O:60][CH3:61])[CH:56]=4)[O:51][C:50]=3[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[CH:45][CH:44]=2)[CH2:42][CH2:41][CH2:40]1)([CH3:35])([CH3:34])[CH3:33]
Reactant: COc1cc2c(=O)c(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)oc2cc1Br
Reactant: NC(=O)c1ccc2c(=O)c(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)oc2c1
Product: COc1cc2c(=O)c(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)oc2cc1C(N)=O
Yield: 27 %

Procedure:
Following the procedure used to prepare 3-[4-(1-amino-cyclobutyl)-phenyl]-4-oxo-2-phenyl-4H-chromene-7-carboxylic acid amide, {1-[4-(7-bromo-6-methoxy-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester was reacted to give the title compound as a colourless oil (22 mg, 27%). LCMS (Method B): RT=4.17 min, [M+H]+=541.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([N:17]=[C:18](Cl)[C:19]([F:22])([F:21])[CH3:20])[CH:5]=1.[N-:25]=[N+:26]=[N-:27].[Na+]>C(#N)C>[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([N:17]2[C:18]([C:19]([F:22])([F:21])[CH3:20])=[N:27][N:26]=[N:25]2)[CH:5]=1
Reactant: COC(=O)c1cc(N=C(Cl)C(C)(F)F)cc(-c2ccc(C)cn2)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)c1cc(-c2ccc(C)cn2)cc(-n2nnnc2C(C)(F)F)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 97.2 %

Procedure:
3-(1-Chloro-2,2-difluoro-propylideneamino)-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester (0.611 g, 1.732 mmol) and NaN3 (0.225 g, 3.464 mmol) were added to 10 mL acetonitrile, and the mixture was stirred at room temperature for 90 minutes. Solvent was removed under reduced pressure and the residue was partitioned between water and EtOAc. The combined organic layers were washed with water, dried (MgSO4), filtered and concentrated under reduced pressure to give 0.605 g of 3-[5-(1,1-Difluoro-ethyl)-tetrazol-1-yl]-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester as a white powder, MS (M+H)=360.
Reaction SMILES: [C:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[CH:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>O1CCCC1.CO>[OH:3][CH:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([N:23]5[CH2:31][C:30]6[C:25](=[CH:26][C:27]([O:32][CH3:33])=[CH:28][CH:29]=6)[C:24]5=[O:34])[C:18]=4[CH3:35])=[CH:15][N:14]=[C:13]([C:36]([NH2:38])=[O:37])[C:9]=3[NH:10]2)=[CH:6][CH:5]=1)[CH3:2]
Reactant: COc1ccc2c(c1)C(=O)N(c1cccc(-c3cnc(C(N)=O)c4[nH]c5cc(C(C)=O)ccc5c34)c1C)C2
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc2c(c1)C(=O)N(c1cccc(-c3cnc(C(N)=O)c4[nH]c5cc(C(C)O)ccc5c34)c1C)C2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 38.2 %

Procedure:
To a cloudy solution of 7-acetyl-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (62 mg, 0.123 mmol) in tetrahydrofuran (5 mL) and methanol (15 mL) at 0° C. was added sodium borohydride (23.25 mg, 0.614 mmol) in one portion. The mixture was stirred at room temperature for 30 min and then the reaction was quenched with ice cold water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with dichloromethane (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (24.8 mg, 0.047 mmol, 38.6% yield) as a white solid. LCMS (M+H)+=507.24. 1H NMR (500 MHz, DMSO-d6) δ: 11.77 (s, 1H), 8.32 (s, 1H), 8.23 (s, 1H), 7.83 (d, J=11.6 Hz, 1H), 7.75 (s, 1H), 7.67 (d, J=6.9 Hz, 1H), 7.60 (d, J=8.3 Hz, 1H), 7.54 (m, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.32 (m, 1H), 7.27-7.23 (m, 2H), 7.08 (dd, J1=12.9 Hz, J2=8.5 Hz, 1H), 5.26 (m, 1H), 4.85 (m, 1H), 4.96 (d, J=16.9 Hz, 1H), 4.86 (d, J=16.9 Hz, 1H), 3.86 (s, 3H), 1.88 (s, 3H), 1.38 (d, J=6.4 Hz, 3H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N+:14]([O-:16])=[O:15])[CH2:4][CH:3]1[CH2:17][OH:18].[H-].[Na+].[CH3:21]I>CN(C=O)C>[CH3:21][O:18][CH2:17][CH:3]1[CH2:4][N:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N+:14]([O-:16])=[O:15])[CH2:6][CH2:7][N:2]1[CH3:1]
Reactant: CN1CCN(c2ccncc2[N+](=O)[O-])CC1CO
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCC1CN(c2ccncc2[N+](=O)[O-])CCN1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 32 %

Procedure:
To (1-methyl-4-(3-nitropyridin-4-yl)piperazin-2-yl)methanol (prepared according to methods similar to the one depicted in Step 1 of Preparation N-1) (250 mg, 0.9910 mmol) in DMF (2 mL) at 0° C. was added NaH (59.43 mg, 1.486 mmol). The reaction mixture was stirred for 10 min before MeI (281.3 mg, 123.40 μL, 1.982 mmol) was added dropwise. The reaction mixture was allowed to warm to RT and was stirred for 2 hours. The reaction mixture was loaded on a pre-washed SCX column, rinsed with MeOH and the product was released with methanolic ammonia. The ammonia extracts were concentrated under reduced pressure. The residue was purified by column chromatography on silica, eluting with 1-15% MeOH:DCM yielding 2-(methoxymethyl)-1-methyl-4-(3-nitropyridin-4-yl)piperazine (84 mg, 32%). MS (ES+) 237.1.
Reaction SMILES: [Br:1][C:2]1[CH:19]=[CH:18][C:5]([N:6]([CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:7][CH:8]([CH3:10])[CH3:9])=[C:4]([CH:20]=[O:21])[CH:3]=1.[C:22](=O)([O-])[O-].[K+].[K+].IC.O>CN(C=O)C>[Br:1][C:2]1[CH:19]=[CH:18][C:5]([N:6]([CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:22])=[O:16])[CH2:7][CH:8]([CH3:10])[CH3:9])=[C:4]([CH:20]=[O:21])[CH:3]=1
Reactant: CC(C)CN(CCCCC(=O)O)c1ccc(Br)cc1C=O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)CCCCN(CC(C)C)c1ccc(Br)cc1C=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
To a suspension of 5-(4-bromo-2-formyl-N-isobutylanilino)pentanoic acid (15.0 g), potassium carbonate (7.0 g) in DMF (50 ml) was added dropwise a solution of iodomethane (8.4 g) in DMF (10 ml) at 0° C. under a nitrogen atmosphere. The mixture was warmed to room temperature, and stirred for 2 hours under a nitrogen atmosphere. After addition of water, the solution was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to hexane:ethyl acetate=1:1) to obtain brown oil of methyl 5-(4-bromo-2-formyl-N-isobutylanilino)pentanoate (13.1 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[CH:5][C:4]=1[CH:13]=[CH:14]C.BrN1[C:21](=[O:22])CCC1=O.O>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([O:11][CH3:12])=[CH:5][C:4]=1[CH:13]([CH3:14])[CH:21]=[O:22]
Reactant: CC=Cc1cc(OC)c(OC)cc1OC
Reactant: O=C1CCC(=O)N1Br
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Br-]
Solvent: O
Solvent: CS(C)=O
Product: COc1cc(OC)c(C(C)C=O)cc1OC
Yield: 45 %

Procedure:
A mixture of 2,4,5 trimethoxy phenyl propene (1 mmol), N-bromosuccinimide (1.5 mmol), water (12 ml), DMSO (3 ml), cetyltrimethyl ammonium bromide (0.3 mmol) was taken in a 100 ml Erlenmeyer flask fitted with loose funnel at the top. The flask was shaken well and placed inside the multimode microwave oven and irradiated (900 W) for 8 minutes in parts. After completion of reaction, the reaction mixture was worked up as in example-1 to provide the corresponding 2-(2,4,5 trimethoxy phenyl)propionaldehyde (45% yield) whose spectral data matched with that mentioned in example-1.
Reaction SMILES: [Cl:1][C:2]1[S:17][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:4]=2[C:3]=1[CH3:18].Cl[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[O:27][CH3:28]>>[CH3:28][O:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH2:20][N:14]1[CH2:13][CH2:12][CH:11]([NH:10][C:9]2[C:4]3[C:3]([CH3:18])=[C:2]([Cl:1])[S:17][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:16][CH2:15]1
Reactant: COc1ccccc1CCl
Reactant: Cc1c(Cl)sc2ncnc(NC3CCNCC3)c12
Product: COc1ccccc1CN1CCC(Nc2ncnc3sc(Cl)c(C)c23)CC1

Procedure:
The title compound was prepared (115 mg, 85%) from 6-chloro-5-methyl-N-(piperidin-4-yl)thieno[2,3-d]pyrimidin-4-amine (95 mg, 0.336 m. mol) and 1-(chloromethyl)-2-methoxybenzene (58 mg, 0.37 m. mol) by following the general procedure described for Preparation 12. 1H NMR (400 MHz, CDCl3):δ 8.40 (s, 1H), 7.35 (m, 1H), 7.25 (m, 1H), 6.95 (m, 1H), 6.85 (d, 1H), 5.35 (d, 1H), 4.25 (m, 1H), 3.85 (s, 3H), 3.60 (s, 2H), 2.90 (m, 2H), 2.50 (s, 3H), 2.35 (m, 2H), 2.10 (m, 2H), 1.40 (m, 2H). MS (ESI) m/z: Calculated: 402.94; Observed: 403.2 (M++1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:14]1(C)C=CC(S(O)(=O)=O)=C[CH:15]=1>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C1(c2cccc(Br)c2)CC1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: CCOC(=O)C1(c2cccc(Br)c2)CC1
Reaction time: 2 h
Yield: 435.8 %

Procedure:
1-(3-Bromophenyl)cyclopropanecarboxylic acid (976 mg, 4.05 mmol) was dissolved in ethanol (20 mL) and p-toluenesulfonic acid (139 mg, 0.810 mmol) was added. The reaction mixture was heated at reflux for 15 h. The temperature of the oil bath was increased from 80° C. to 110° C. and the reaction mixture was stirred for 2 h at that temperature, after which the mixture was cooled and the solvent was removed under reduced pressure. The crude material was purified via flash chromatography (pentane:ethyl acetate 9:1) to afford ethyl 1-(3-bromophenyl)cyclopropanecarboxylate as a colorless oil (950 mg, 87.2%). 1H NMR (400 MHz, CDCl3) δ 1.13-1.20 (m, 5H), 1.57-1.62 (m, 2H), 4.10 (q, 2H), 7.17 (s, 1H), 7.27 (s, 1H), 7.38 (s, 1H), 7.47-7.50 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[C:15]([C:17]([OH:19])=O)[CH:16]=[C:11]3[CH:10]=[CH:9]2)=[CH:5][CH:4]=1.F[C:23]1[C:28]([NH2:29])=[CH:27][CH:26]=[C:25]([F:30])[N:24]=1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.N1C=CC=CC=1>[F:30][C:25]1[N:24]=[C:23]2[O:19][C:17]([C:15]3[CH:16]=[C:11]4[CH:10]=[CH:9][N:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:21][CH:20]=5)[C:12]4=[N:13][CH:14]=3)=[N:29][C:28]2=[CH:27][CH:26]=1
Reactant: COc1ccc(Cn2ccc3cc(C(=O)O)cnc32)cc1
Reactant: Nc1ccc(F)nc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: COc1ccc(Cn2ccc3cc(-c4nc5ccc(F)nc5o4)cnc32)cc1
Temperature: 150 °C

Procedure:
To a stirred solution of 1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (47 mg, 0.17 mmol) in CH2Cl2 (2 mL) was added 1-chloro-N,N-2-trimethylpropenylamine (45 μL, 0.34 mmol). Following formation of the resulting acid chloride, the reaction mixture was concentrated affording a residue that was dissolved in pyridine (2 mL) before 2,6-difluoro-pyridin-3-ylamine (20 mg, 0.15 mmol) was added in one portion. After an additional 30 minutes the reaction mixture was concentrated to dryness affording a residue, to which was added DMF (2 mL) and K2CO3 (64 mg, 0.46 mmol). The resulting mixture was heated by microwave to 150° C. for 10 min, after which the resulting mixture was filtered and concentrated, affording 5-fluoro-2-[1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-oxazolo[5,4-b]pyridine as a crude residue which was subsequently used without further purification. ES MS (M+H+)=375.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][N:14]1[CH:18]=[C:17]([N+:19]([O-])=O)[CH:16]=[N:15]1>[Pd].CCO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][N:14]1[CH:18]=[C:17]([NH2:19])[CH:16]=[N:15]1
Reactant: COc1ccc2[nH]cc(CCn3cc([N+](=O)[O-])cn3)c2c1
Agent: [Pd]
Solvent: CCO
Product: COc1ccc2[nH]cc(CCn3cc(N)cn3)c2c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a round bottom flask 5-methoxy-3-(2-(4-nitro-1H-pyrazol-1-yl)ethyl)-1H-indole (2.11 g, 7.37 mmol), Pd/C (200 mg) and EtOH (35 mL, degassed) was added. The flask was evacuated and backfilled with H2 and the reaction mixture was stirred under H2-atmosphere at rt for 18 h. The reaction mixture was filtered over celite, washed with EtOH and the solvent was removed under reduced pressure to yield the title compound as a red oil, which was used in the next step without further purification. LC-MS conditions B: tR=0.42 min, [M+H]+=257.16.
Reaction SMILES: I/[CH:2]=[CH:3]\[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[C:10]1([C:16]#[CH:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[C:16]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)#[C:17][CH:2]=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCC/C=C\I
Reactant: C#Cc1ccccc1
Product: CCCCCCC=CC#Cc1ccccc1

Procedure:
The modified procedure was used to convert (Z)-1-Iodo-oct-1-ene and phenyl acetylene to the title product. Purification by flash chromatography (hexane as the eluent) gave the analytically pure product as a colorless oil (420 mg, 98% yield). 1H NMR (400 MHz, CDCl3) δ 7.44-7.41 (m, 2H), 7.29-7.27 (m, 3H), 5.99-5.92 (m, 1H), 5.67-5.65 (d, J=10.7, 1H), 2.42-2.36 (m, 2H), 1.46-1.43 (m, 2H), 1.37-1.29 (m, 6H), 0.89-0.86 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 144.36, 131.42, 128.30, 127.96, 123.82, 109.06, 93.46, 86.57, 31.76, 30.45, 28.96, 28.91, 22.70, 14.16. Anal. Calcd. for C16H20: C, 90.51; H, 9.49; Found C, 90.24; H, 9.47.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1.[Cl:22][CH2:23][C:24](=O)[CH2:25][OH:26]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:24]([CH2:25][OH:26])[CH2:23][Cl:22])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1
Reactant: NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Reactant: O=C(CO)CCl
Solvent: C1CCOC1
Product: OCC(CCl)=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1

Procedure:
In the manner given in Example 1, 7-chloro-2-hydrazino-5-(o-chlorophenyl)-3H-1,4-benzodiazepine in tetrahydrofuran can be treated with 1-chloro-3-hydroxypropanone under nitrogen to give 7-chloro-2-[[2-chloro-1-(hydroxymethyl)ethylidene]hydrazino]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C(CC[CH:12]1[CH2:17][N:16]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(O)=O.C[CH2:33][O:34]CC>>[OH:34][CH2:33][CH:12]1[CH2:17][N:16]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CCOCC
Reactant: O=C(O)CCC1CN(Cc2ccccc2)CCN1Cc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: OCC1CN(Cc2ccccc2)CCN1Cc1ccccc1
Temperature: -5 °C
Yield: 86 %

Procedure:
In a dry flask were carefully placed 5.67 g (150 mmol) of lithium aluminum hydride to which were added 110 ml of absolute ether. The suspension was flushed with nitrogen and cooled to -5° C. Then a solution of 25 g (73.0 mmol) of 2-carboxyethyl-1,4-di-phenylmethyl piperazine in 110 ml of absolute ether was added dropwise. After complete addition the suspension was heated under reflux for three hours, cooled in an ice-bath. Excess of hydride was carefully destroyed with 6.3 ml of water. Insoluble material was filtered off and the ether layer was washed with water and dried over magnesium sulfate. After removing of the solvent it was obtained 18.85 g. (86%) of title compound. MP 77° C.
Reaction SMILES: [Cl:1][C:2]1[N:20]=[CH:19][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[NH:15][CH:16]=[CH:17][N:18]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH:27](I)([CH3:29])[CH3:28]>CN(C)C=O.O.CCOC(C)=O>[Cl:1][C:2]1[N:20]=[CH:19][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:27]([CH3:29])[CH3:28])[CH:17]=[CH:16][N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1
Reactant: Clc1cc2c(cn1)-c1nc(-c3ncc[nH]3)cn1CCO2
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)n1ccnc1-c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Temperature: 50 °C
Yield: 47.7 %

Procedure:
To a solution of 9-chloro-2-(1H-imidazol-2-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine (0.402 g, 1.4 mmol) in N,N-dimethylformamide (9.6 mL) was added Cs2CO3 (0.6 g, 2.0 mmol) followed by isopropyl iodide (0.2 mL, 2 mmol). The reaction mixture was heated at 50° C. for a 20 h period. The mixture was subsequently cooled to room temperature and diluted with water and EtOAc. The mixture was extracted twice with EtOAc, dried over MgSO4, filtered and concentrated. The resultant residue was purified by flash column chromatography (0-10% MeOH in dichloromethane). This procured 0.22 g (48% yield) of 9-chloro-2-(1-isopropyl-1H-imidazol-2-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine which was combined with L-prolinamide (0.152 g, 1.33 mmol) in N,N-dimethylacetamide (6.7 mL) and sealed in a pressure vessel. The mixture was heated at 150° C. was heated for 40 h at which point an additional amount of L-prolinamide (0.152 g, 1.33 mmol) was added and the mixture was continued to be heated for 12 h. Only 50% conversion was observed at the end of this period and heating was discontinued and the material was purified by rp-HPLC eluting with 0.1% NH4OH in acetonitrile to provide 19.8 mg (8% yield) of 377. MS (ESI+) m/z 408.2 (M+H+), calcd. 408.5. 1H NMR (400 MHz, DMSO) δ 9.03 (s, 1H), 7.58 (s, 1H), 7.43-7.26 (m, 2H), 6.89 (d, J=1.0 Hz, 2H), 5.94 (s, 1H), 5.72 (dt, J=13.6, 6.8 Hz, 1H), 4.56-4.38 (m, 4H), 4.29 (d, J=8.0 Hz, 1H), 3.59 (s, 1H), 2.17 (d, J=8.9 Hz, 1H), 1.98 (dd, J=31.1, 24.1 Hz, 4H), 1.44 (d, J=4.2 Hz, 6H).