Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([OH:17])(=O)=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.CN(C)C=O.S(Cl)([Cl:25])=O>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([Cl:25])(=[O:17])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=S(=O)(O)c1ccc(-c2ccc(Br)cc2)cc1
Solvent: CN(C)C=O
Product: O=S(=O)(Cl)c1ccc(-c2ccc(Br)cc2)cc1
Temperature: 25 °C

Procedure:
To a solution of 4′-bromobiphenyl-4-sulfonic acid 13a (18.8 g, 78.1 mmol) in thionyl chloride (150 mL) is added a catalytic amount of N,N-dimethylformamide (0.3 mL). The reaction mixture is heated to reflux for 4 hr. The mixture is then cooled to room temperature, and concentrated under reduced pressure. Toluene is then added and the mixture is concentrated under reduced pressure. The solid crude product is then recrystallized with ethyl acetate and hexanes to give the solid desired product.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[N:13]([C:21]4[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][N:22]=4)[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=3)[O:8][C:7](=[O:28])[C:6]=2[CH:5]=[C:4]2[NH:29][CH:30]=[N:31][C:3]=12.[CH:32]([NH2:35])([CH3:34])[CH3:33]>>[CH:32]([NH:35][C:7]([C:6]1[C:11]([NH:10][C:9]([C:12]2[N:13]([C:21]3[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][N:22]=3)[N:14]=[C:15]([C:17]([F:19])([F:20])[F:18])[CH:16]=2)=[O:8])=[C:2]([Cl:1])[C:3]2[N:31]=[CH:30][NH:29][C:4]=2[CH:5]=1)=[O:28])([CH3:34])[CH3:33]
Reactant: CC(C)N
Reactant: O=c1oc(-c2cc(C(F)(F)F)nn2-c2ncccc2Cl)nc2c(Cl)c3nc[nH]c3cc12
Product: CC(C)NC(=O)c1cc2[nH]cnc2c(Cl)c1NC(=O)c1cc(C(F)(F)F)nn1-c1ncccc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
See step f) of example H2 with 4-chloro-6-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-1H-7-oxa-1,3,5-triaza-cyclopenta[b]naphthalen-8-one as starting material and 2 equivalents of isopropylamine. After overnight stirring at ambient temperature, 2 equivalents of amine were added and the reaction is stopped after 5 hours. After purification by flash chromatography on silica gel, a white solid is obtained in 50% yield. m.p.: 200-203° C.; LC/MS: 526/528 (M+1)+.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N+:9]([O-:11])=[O:10].[NH2:12][CH2:13][CH:14]([OH:17])[CH2:15][OH:16]>CN1CCCC1=O>[OH:17][CH:14]([CH2:15][OH:16])[CH2:13][NH:12][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: NCC(O)CO
Reactant: O=[N+]([O-])c1c(Cl)cccc1Cl
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1c(Cl)cccc1NCC(O)CO

Procedure:
0.2 mole (38.4 g) of 2,6-dichloronitrobenzene and 0.6 mole (54.6 g) of 3-aminopropane-1,2-diol in 200 ml of 1-methyl-2-pyrrolidone are heated to 80° C. The reaction mixture is diluted with ice. The product expected precipitates. After recrystallizing from isopropanol, it melts at 126° C.
Reaction SMILES: F[C:2]1[C:7]([CH:8]=O)=[C:6]([I:10])[CH:5]=[CH:4][N:3]=1.O.[NH2:12][NH2:13]>O>[I:10][C:6]1[CH:5]=[CH:4][N:3]=[C:2]2[NH:12][N:13]=[CH:8][C:7]=12
Reactant: O=Cc1c(I)ccnc1F
Reactant: NN
Solvent: O
Product: Ic1ccnc2[nH]ncc12
Temperature: 25 °C
Reaction time: 5 h

Procedure:
2-Fluoro-4-iodo-3-pyridinecarbaldehyde (from Asymchem) (0.97 g) was added portionwise over 5 min to hydrazine hydrate (5 ml). The resulting suspension was stirred at room temperature for 5 h. Water (10 ml) was added and the solid was filtered and washed with further water to give title compound, 664 mg.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][O:3][CH2:4][CH2:5][OH:6].C(N(CC)CC)C.Cl[C:16](Cl)([O:18]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[O:6]1[CH2:5][CH2:4][O:3][CH2:2][CH2:1][O:7][C:16]1=[O:18]
Reactant: OCCOCCO
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1OCCOCCO1

Procedure:
The procedure of Example 1 was followed using diethylene glycol (8.9 g, 83.9 mmol), triethylamine (24.0 mL, 167.8 mmol), dry THF (600 mL) and triphosgene (8.3 g, 28.8 mmol). The filtrate was concentrated yielding only oligomeric compounds.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[C:14]([CH2:19]O)[CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Br)(Br)(Br)[Br:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)C>C(Cl)Cl>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[C:14]([CH2:19][Br:22])[CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrC(Br)(Br)Br
Reactant: O=S(=O)(c1ccccc1)n1ccc2c(CO)cccc21
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOCC
Product: O=S(=O)(c1ccccc1)n1ccc2c(CBr)cccc21
Reaction time: 1 h
Yield: 86.4 %

Procedure:
To a stirred solution of 0.78 g (2.71 mmol) of alcohol (30) and 1.13 g (3.41 mmol) of carbontetrabromide in 10 ml of CH2Cl2 at 0° C. was added 1.07 g (4.08 mmol) of triphenylphosphine. After one hour at 0° C., the solvent was removed under reduced pressure. The residue was flash chromatographed on silica, eluting CH2Cl2. After trituration with diethyl ether there was obtained 0.82 g (80% yield) of 1-benzenesulfonyl-4-bromomethyl-1H-indole (31) as a white solid, m.p. 127°-128° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH:13]([CH3:16])[CH2:14][OH:15])=[CH:9][CH:8]=[CH:7][CH:6]=2.[C:17](OC(OCC)OCC)(=O)C.[OH-].[NH4+]>O>[CH3:16][CH:13]([N:12]1[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=[CH:17]1)[CH2:14][OH:15]
Reactant: CC(CO)Nc1c(N)cnc2ccccc12
Reactant: CCOC(OCC)OC(C)=O
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: CC(CO)n1cnc2cnc3ccccc3c21

Procedure:
2-[(3-Amino-4-quinolinyl)amino]-1-propanol (0.113 mole) as a crude reaction product obtained by the method of Example 4, was mixed with a 20 percent molar excess of diethoxymethyl acetate (22.3g, 0.136 mole) and heated for 0.75 hour. To the mixture was added 150 mL of water. The resulting mixture was made basic with concentrated ammonium hydroxide, and extracted first with ethyl acetate, then with chloroform. The extracts were combined, dried over magnesium sulfate, and evaporated, slurried in 1:1 chloroform/diethyl ether and separated by filtration to provide the solid product, beta-methyl-1H-imidazo[4,5-c]-quinoline-1-ethanol, m.p. 170°-174° C. after recrystallization from ethanol with treatment with decolorizing carbon. Analysis: Calculated for C13H13N3O: %C, 68.7; %H, 5.8; %N, 18.5; Found: %C, 68.5; %H, 5.8; %N, 18.5.
Reaction SMILES: [C:1]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17](=[O:27])[CH2:18][P:19]([O:24][CH2:25][CH3:26])([O:21][CH2:22][CH3:23])=[O:20])[CH:12]1[C:28]([OH:30])=[O:29])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C1(NC2CCCCC2)CCCCC1>CN(C)C=O>[C:1]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17](=[O:27])[CH2:18][P:19]([O:24][CH2:25][CH3:26])([O:21][CH2:22][CH3:23])=[O:20])[CH:12]1[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]
Reactant: BrCc1ccccc1
Reactant: CCOP(=O)(CC(=O)C1CCCN(C(=O)OCc2ccccc2)C1C(=O)O)OCC
Agent: C1CCC(NC2CCCCC2)CC1
Solvent: CN(C)C=O
Product: CCOP(=O)(CC(=O)C1CCCN(C(=O)OCc2ccccc2)C1C(=O)OCc1ccccc1)OCC
Temperature: 25 °C
Yield: 19 %

Procedure:
Dissolve N-carbobenzoxy-3[(diethoxyphosphinyl)acetyl]-piperidine-2-carboxylic acid (36.4 mmol) in dimethylformamide (200 mL) and place under a nitrogen atmosphere. Add benzyl bromide (10.5 mL), 81 mmol) and dicyclohexyl amine (16.2 mL, 89 mmol) and heat to 65° C. Allow to cool slowly to room temperature and filter. Pour the filtrate into water (11/2 L) and extract with ethyl acetate (2×500 mL). Combine the organic phases and dry (MgSO4). Evaporate the solvent in vacuo to give a brown oil. Purify by flash chromatography (ethyl acetate) to give the title compound as a yellow oil (3.6 g, 19%).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:11][C:12]1[C:13]([Br:21])=[N:14][C:15]([O:19][CH3:20])=[CH:16][C:17]=1[CH3:18]>C(Cl)Cl>[Br:21][C:13]1[C:12]([NH:11][C:4]([C:3]2[C:2]([Cl:1])=[N:10][CH:9]=[CH:8][CH:7]=2)=[O:5])=[C:17]([CH3:18])[CH:16]=[C:15]([O:19][CH3:20])[N:14]=1
Reactant: O=C(Cl)c1cccnc1Cl
Reactant: COc1cc(C)c(N)c(Br)n1
Solvent: ClCCl
Product: COc1cc(C)c(NC(=O)c2cccnc2Cl)c(Br)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.6 %

Procedure:
2-Chloronicotinoyl chloride (3.5 g) was added to a solution of 3-amino-2-bromo-6-methoxy-4-methylpyridine (4.5 g) in methylene chloride, and the resulting mixture was stirred overnight at room temperature, and triturated with diisopropyl ether. The precipitated solid was filtered to give 6.0 g of the title compound, suitable for use in the next reaction.
Reaction SMILES: [C:1]1([CH:7]([CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:8]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.OS([O-])(=O)=O.[K+]>C1COCC1.O>[C:1]1([CH:7]([CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:8][N:20]2[C:16](=[O:26])[C:17]3[C:18](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:19]2=[O:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCC(CN1CCCC1)c1ccccc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=C1c2ccccc2C(=O)N1CC(CN1CCCC1)c1ccccc1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a solution of 2-phenyl-3-pyrrolidin-1-yl propan-1-ol (3.4 mmol) in THF (10 mL) is successively added phthalimide (4.1 mmol), triphenylphosphine (5.1 mmol) and diethyl azodicarboxylate (5.1 mmol) at 0° C., then the mixture is stirred at 0° C. for 1.5 h. After dilution with water, the mixture is acidified to pH<3 with aq. KHSO4 then washed with AcOEt. The aqueous layer basified to pH>11 with sat aq. NaHCO3 then extracted with AcOEt. The organic extracts are washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue is triturated with ether to give 2-(2-phenyl-3-pyrrolidin-1-yl propyl)isoindole-1,3-dione, which is directly used for the next reaction without further purification.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[Cl:1][C:2]1[N:3]=[N:4][C:5]([N:24]2[CH2:25][CH2:26][N:21]([C:16]3[N:15]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH2:22][CH2:23]2)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: c1cnc(N2CCNCC2)nc1
Reactant: Clc1cc(-c2ccccc2)c(Cl)nn1
Product: Clc1nnc(N2CCN(c3ncccn3)CC2)cc1-c1ccccc1
Temperature: 80 °C
Reaction time: 12 h
Yield: 86.7 %

Procedure:
A mixture of 3,6-dichloro-4-phenylpyridazine (1.35 g, 6 mmol), 1-(2-pyrimidyl)piperazine (1.2 g, 6.0 mmol) in 10 ml of 1-BuOH was heated with stirring at 80° C. for 12 h. The solvent was removed by evaporation in vacuo, the residue was treated with water to give a suspension. The solid was then filtered off, washed with water, dried over filter funnel in vacuo to give white solid (1.8 g, 5.2 mmol, yield 86.0%). ESI-MS: m/z 353.9.
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:27]=[CH:26][C:21]([C:22](OC)=[O:23])=[CH:20][CH:19]=1)[CH2:2][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][CH3:16].[NH2:28][NH2:29]>C(O)COCCO>[CH2:1]([NH:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([NH:28][NH2:29])=[O:23])=[CH:20][CH:19]=1)[CH2:2][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][CH3:16]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC)cc1
Reactant: NN
Solvent: OCCOCCO
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)NN)cc1
Temperature: 125 °C
Reaction time: 3 h

Procedure:
A mixture of 6.59 g. of methyl 4-(hexadecylamino)benzoate, 100 ml. of diethylene glycol, and 45 ml. of 95% hydrazine was heated and stirred in an oil bath at 125° C. under nitrogen for 3 hours and cooled to room temperature. The separated crystals were collected in a suction funnel and washed with ethanol several times and dried in air to give 7.6 g. of white crystals. The crystals were dissolved in 140 ml. of boiling ethanol and recrystallized to give 5.95 g. of fine white crystals, melting point 154°-156° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH3:10])[C:5]([N+:11]([O-])=O)=[CH:4][CH:3]=1.[Cl-].[NH4+]>C(O)C.O.CCOC(C)=O.[Fe]>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH3:10])[C:5]([NH2:11])=[CH:4][CH:3]=1
Reactant: CCNc1nc(Cl)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: O
Product: CCNc1nc(Cl)ccc1N
Temperature: 140 °C
Yield: 99.9 %

Procedure:
To a solution of 6-chloro-N-ethyl-3-nitropyridin-2-amine (1.82 g, 9.04 mmol) in ethanol (20 mL) is added iron powder (2.52 g, 45.2 mmol) and a solution of ammonium chloride (2.42 g, 45.2 mmol) in H2O (8 mL). The mixture is heated in a microwave reactor at 140° C. for 30 min. The mixture is diluted with EtOAc, filtered and evaporated to afford the title compound as a brown oil (1.55 g, 100%) which was used in the next step without purification.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[S:8][CH:9]=[CH:10][C:11]=1[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]2[NH:19][CH:20]=[CH:21][C:14]=12)=[O:6].[C:22]1([S:28](Cl)(=[O:30])=[O:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:22]1([S:28]([NH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]2[S:8][CH:9]=[CH:10][C:11]=2[NH:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]3[NH:19][CH:20]=[CH:21][C:14]=23)=[O:6])(=[O:30])=[O:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: NCCNC(=O)c1sccc1Nc1ccnc2[nH]ccc12
Product: O=C(NCCNS(=O)(=O)c1ccccc1)c1sccc1Nc1ccnc2[nH]ccc12

Procedure:
This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid (2-amino-ethyl)-amide using benzenesulfonyl chloride instead of benzoyl chloride. LCMS (ESI) 442 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (1H, br. s.) 10.25 (1H, s) 8.05 (1H, t, J=5.76 Hz) 8.00 (1H, d, J=5.47 Hz) 7.70-7.81 (4H, m) 7.49-7.62 (3H, m) 7.45 (1H, d, J=5.47 Hz) 7.25-7.32 (1H, m) 6.81 (1H, d, J=5.47 Hz) 6.39 (1H, dd, J=3.42, 1.85 Hz) 3.21-3.28 (2H, m) 2.82-2.93 (2H, m)
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([NH:12][C:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:7][CH:6]=[CH:5]2.Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH2:36][N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][CH:23]=1.[OH-].[K+]>CN(C=O)C.N1C=CC=CC=1.C(Cl)Cl.O.[Cu]>[CH3:33][O:32][C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][C:28]=1[O:34][CH2:35][CH2:36][N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1)[N:25]=[CH:24][CH:23]=[C:22]2[O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([NH:12][C:13](=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[CH:7][CH:6]=[CH:5]2
Reactant: COc1cc2c(Cl)ccnc2cc1OCCN1CCCC1
Reactant: O=C(Nc1cccc2cc(O)ccc12)c1ccccc1
Agent: [Cu]
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: COc1cc2c(Oc3ccc4c(NC(=O)c5ccccc5)cccc4c3)ccnc2cc1OCCN1CCCC1
Temperature: 120 °C

Procedure:
To a microwaveable vial containing 0.300 g (0.0011 mmol) of N-(6-hydroxy-naphthalen-1-yl)-benzamide in 1.5 mL DMF and 1.5 mL pyridine, was added 0.858 g (0.0028 mmol) of 4-chloro-6-methoxy-7-(2-pyrrolidin-1-yl-ethoxy)-quinoline. Copper grind was added (5 mmol %) to the mixture, along with 0.158 g (0.0025 mmol) KOH pellets. The vial was heated in a microwave for 18 min at 120° C., (60 Watts of constant power, powermax, CEM). The mixture was diluted with CH2Cl2 and water, then transferred to a seperatory funnel. The organics were extracted 3× with CH2Cl2. Then combined all organics, dried over Na2SO4, filtered, and concentrated in-vacuo. The crude was purified by reverse-phase HPLC. A tan oil was collected, which was the titled product. MS (ESI pos. ion) m/z: 534 (M+H). Calc'd for C33H31N3O4−533.23.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[C-:13]#[N:14].[K+].CS(C)=O>O>[C:13]([CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])#[N:14]
Reactant: [C-]#N
Reactant: CC(C)(C)OC(=O)NCCCBr
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: CC(C)(C)OC(=O)NCCCC#N
Temperature: 90 °C
Yield: 54.3 %

Procedure:
To a 250 mL of round-bottom flask was added tert-butyl 3-bromopropylcarbamate (4.0 g, 17 mmol) (commercially available from 3B Scientific Corporation Product List Order Number 3B3-073730), potassium cyanide (1.5 mL, 20 mmol) and 100 mL of DMSO. The reaction mixture was heated at 90° C. for 16 hours. The mixture was then diluted with 100 mL of water, and extracted with 100 mL of EtOAc twice. The extracts were combined, concentrated, and purified by flash chromatography on silica gel (40% EtOAc/hexane) to give tert-butyl 3-cyanopropylcarbamate (1.7 g, 55% yield). MS m/z: 185 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 4.70 (br s, 1H), 3.25 (q, J=6.65 Hz, 2H), 2.40 (t, J=7.24 Hz, 2H), 1.84-1.91 (m, 2H), 1.45 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH:4]=O.[CH:11]1([NH2:14])[CH2:13][CH2:12]1>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH2:4][NH:14][CH:11]1[CH2:13][CH2:12]1
Reactant: NC1CC1
Reactant: O=Cc1c(F)cccc1Cl
Product: Fc1cccc(Cl)c1CNC1CC1

Procedure:
Synthesized according to typical procedure J from 2-chloro-6-fluorobenzaldehyde and cyclopropylamine.
Reaction SMILES: [N:1]1([CH2:4][C@:5]23[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:6]2[C@@H:7]2[C@@:20]([CH3:23])([CH2:21][CH2:22]3)[C@@:19]3([CH3:24])[C@@H:10]([C@:11]4([CH3:36])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8]2)CC1.Br[CH2:44][CH2:45][OH:46]>>[OH:46][CH2:45][CH2:44][NH:1][CH2:4][C@:5]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:6]1[C@@H:7]1[C@@:20]([CH3:23])([CH2:21][CH2:22]2)[C@@:19]2([CH3:24])[C@@H:10]([C@:11]3([CH3:36])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]2[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=2)=[CH:13][CH2:12]3)[CH2:9][CH2:8]1
Reactant: OCCBr
Reactant: C=C(C)[C@@H]1CC[C@]2(CN3CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Product: C=C(C)[C@@H]1CC[C@]2(CNCCO)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the general procedures described above for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-ylmethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid using 2-bromoethanol as the alkylating reagent in step 1. The product was isolated as a white solid (21.9 mg, 79.9%). LCMS: m/e 588.9 (MH+), 2.373 min (method 9). 1H NMR (500 MHz, DMSO-d6) δ 7.88 (d, J=8.2 Hz, 2H), 7.23 (d, J=8.2 Hz, 2H), 5.25 (d, J=4.9 Hz, 1H), 4.72 (s, 1H), 4.61 (s, 1H), 3.74 (m, 2H), 3.14 (br. s., 1H), 3.08 (m, 2H), 2.80-2.68 (m, 1H), 2.45 (m, 1H), 2.12-1.94 (m, 2H), 1.93-1.79 (m, 2H), 1.74-1.58 (m, 8H), 1.57-1.29 (m, 8H), 1.28-1.13 (m, 4H), 1.08 (s, 4H) 1.00 (3H, s), 0.96 (3H, s), 0.91 (6H, s).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH3:12])[C:7]([CH2:10][OH:11])=[N:8][CH:9]=1)=[O:4].[H-].[Na+].S(OC)(O[CH3:19])(=O)=O.ClCCl>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH3:12])[C:7]([CH2:10][O:11][CH3:19])=[N:8][CH:9]=1)=[O:4]
Reactant: COS(=O)(=O)OC
Reactant: COC(=O)c1cnc(CO)n1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COCc1ncc(C(=O)OC)n1C
Reaction time: 1 h
Yield: 42 %

Procedure:
A solution of 2-hydroxymethyl-3-methyl-3H-imidazole-4-carboxylic acid methyl ester (250 mg, 1.5 mmol) in dimethylformamide (10 ml) is subsequently treated with sodium hydride (71 mg 60% dispersion in mineral oil, 1.8 mmol) and after 0.5 h with dimethyl sulfate (0.17 ml, 1.8 mmol). After 1 h at ambient temperature, the volatile componantes are removed in vacuo, the residue taken up in ethyl accetate (20 ml) and water (20 ml) and the phases separated. The aqueous phase is extracted twice with ethyl acetate (20 ml each) and the combined organic layers are dryed with magnesium sulfate and evaporated to dryness. Flash chromatography (silica, eluent dichloromethane containing 4% methanol) afforded the title compound as white crystals (42% yield). MS: m/e=185(M+H+), mp 74-77° C.
Reaction SMILES: [C:1]1([C:7]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[NH2:23])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1.CC(C)([O-])C.[K+]>CS(C)=O>[C:1]1([C:7]2[C:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][C:13]=3[NH:23][C:25]3[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=3)[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: Nc1cccc2nc(-c3ccccc3)c(-c3ccccc3)nc12
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccc(Nc2cccc3nc(-c4ccccc4)c(-c4ccccc4)nc23)cc1
Reaction time: 24 h

Procedure:
While agitating 4.0 g (13.4 mmol) of 2,3-diphenyl-5-aminoquinoxaline, 2.1 g (14.9 mmol) of 4-fluoronitrobenzene and 100 ml of dimethylsulfoxide, 5.0 g (44.6 mmol) of potassium t-butoxide was gently added thereto. After completion of the addition, the reaction container was purged with nitrogen, followed by agitation at room temperature for 24 hours. After completion of the reaction, 100 ml of water was added to the container while cooling, and an organic phase was extracted with a chloroform solvent, followed by evaporation of the solvent for concentration to obtain the intended product.
Reaction SMILES: C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].[CH3:15][O:16][C:17]([CH3:30])([CH3:29])[CH2:18][CH2:19][CH:20]1[CH2:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:22](=[O:28])[CH2:21]1>O1CCCC1>[CH3:15][O:16][C:17]([CH3:30])([CH3:29])[CH2:18][CH2:19][CH:20]1[CH2:25][C:24]([CH3:26])([CH3:27])[CH2:23][CH:22]([OH:28])[CH2:21]1
Reactant: COC(C)(C)CCC1CC(=O)CC(C)(C)C1
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(C)(C)CCC1CC(O)CC(C)(C)C1
Reaction time: 16 h

Procedure:
To lithium tri-sec-butylborohydride (2.7 mL of a 1.0 M solution in tetrahydrofuran, 0.0027 mol) cooled to -65~C was added 3-(3-methoxy-3-methylbutyl)-5,5-dimethylcyclohexan-1-one (0.5 g, 0.0022 mol) dissolved in tetrahydrofuran (3.5 mL). The mixture was allowed to stir at 25~C for 16 hours. Workup yielded 3-(3-methoxy-3-methylbut-1-yl)-5,5-dimethylcyclohexan-1-ol, bp1.0 210-21218 C (0.31 g). This compound was determined to possess a warm woody note. NMR(CDC13)δ0.9(s,3H), 1.1 (s,3H), 1.2(s,6H), 1.2-1.4(m,4H), 1.4-1.7(m,6H), 1.7-1.9(m,2H), 3.2(s,3H), 4.2(m, 1H); IR(neat) 3425, 2970, 2940, 1470, 1365, 1080 cm-1 ; MS(m/e) 43, 55, 73, 125, 163, 213, 214.