Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([C:8]1[CH:22]=[CH:21][C:11]([CH2:12]P(=O)(OCC)OCC)=[CH:10][CH:9]=1)([O:5][CH2:6][CH3:7])=[O:4].[CH:23]([C:25]1[C:34]([O:35][CH2:36][CH2:37][CH3:38])=[CH:33][C:32]2[C:31]([CH3:40])([CH3:39])[CH2:30][CH2:29][C:28]([CH3:42])([CH3:41])[C:27]=2[CH:26]=1)=O.Cl>O1CCCC1.CS(C)=O>[CH3:39][C:31]1([CH3:40])[CH2:30][CH2:29][C:28]([CH3:41])([CH3:42])[C:27]2[CH:26]=[C:25](/[CH:23]=[CH:12]/[C:11]3[CH:10]=[CH:9][C:8]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:22][CH:21]=3)[C:34]([O:35][CH2:36][CH2:37][CH3:38])=[CH:33][C:32]1=2
Reactant: CCCOc1cc2c(cc1C=O)C(C)(C)CCC2(C)C
Reactant: CCOC(=O)c1ccc(CP(=O)(OCC)OCC)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: CCCOc1cc2c(cc1/C=C/c1ccc(C(=O)OCC)cc1)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
1.3 g of sodium hydride, 50% in mineral oil, were suspended in 20 ml of abs. dimethyl sulphoxide (DMSO) and treated dropwise at 15° C. with a solution of 8.6 g of diethyl (4-carbethoxybenzyl)-phosphonate in 25 ml of abs. DMSO. The mixture was stirred at room temperature for 1 hour and then a solution of 3.3 g of the above aldehyde in 25 ml of abs. DMSO and 10 ml of tetrahydrofuran was added dropwise thereto. After stirring at 40° C. for 2 hours the mixture was poured into ice-water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. After drying the organic phase with sodium sulphate and evaporation of the solvent the crude product was filtered over a silica gel column (eluent hexane/5% methyl tert.butyl ether). After recrystallization from hexane/ethyl acetate there were obtained 4.4 g of ethyl (E)-4-[2-(5,5,8,8-tetra-methyl-3 -propoxy-5,6,7,8 -tetrahydro-naphthalen-2-yl)vinyl]benzoate in the form of white crystals, melting point 97°-100° C.
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12]C)[CH:7]=1)=[O:5]>Br>[NH2:1][C:2]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[CH:7]=1)=[O:5]
Reactant: COc1cccc(C(=O)c2ccc(Cl)cc2N)c1
Agent: Br
Product: Nc1cc(Cl)ccc1C(=O)c1cccc(O)c1
Yield: 83.3 %

Procedure:
2-Amino-4-chloro-3'-methoxybenzophenone (3.75 g, 14.3 mmol) was dissolved in 90 mL of 48% hydrobromic acid and the solution was heated at refluxed for 12 h. The solvent was removed by rotary evaporation and the resulting red solid was distributed between saturated sodium bicarbonate (200 mL) and CH2Cl2 (250 mL). The aqueous layer was washed with CH2Cl2 (2×100 mL) and the combined organic layers were dried with sodium sulfate, filtered through celite and concentrated in vacuo to afford 2.95 g (83% yield) of 2-amino-4-chloro-3'-hydroxybenzophenone (22b) as a yellow solid: mp 137-138° C., Rf 0.15 (75:25, hexanes/ethyl acetate). 1H NMR (500 MHz, CDCl3); δ 6.16 (b, 2), 6.55 (dd, 1, J=2.0, 8.5), 6.72 (d, 1, J=1.9), 6.99 (dd, 1, J=2.5, 8.1), 7.05 (t, J=2.0), 7.12 (d, 1, J=7.8), 7.30 (t, 1, 7.8), 7.38 (d, 1, J=8.6). 13C NMR (101 MHz): δ 115.6, 116.1, 116.2, 118.4, 120.3, 121.6, 126.1, 129.5, 135.9, 142.2, 154.3. HRMS (FAB, m-nitrobenzyl alcohol) calcd for C13H10CINO2 (M+H) 248.0046, found 248.0484.
Reaction SMILES: [CH2:1]([N:8](C)[C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:19]2[C:20]([CH3:26])=[N:21][N:22]([CH3:25])[C:23]=2[CH3:24])[CH2:10]1)C1C=CC=CC=1.CO>C1COCC1.[Pd]>[CH3:1][NH:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:19]2[C:20]([CH3:26])=[N:21][N:22]([CH3:25])[C:23]=2[CH3:24])[CH2:10]1
Reactant: Cc1nn(C)c(C)c1-c1cccc2c1CC[C@H](N(C)Cc1ccccc1)C2
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CN[C@H]1CCc2c(cccc2-c2c(C)nn(C)c2C)C1
Reaction time: 16 h
Yield: 91.6 %

Procedure:
A solution of (2S)-benzyl-methyl-[5-(1,3,5-trimethyl-1 H-pyrazol-4-yl)-1,2,3,4-tetrahydro-naphthalen-2-yl]-amine (3.70 g, 10.291 mmol) in THF (20 mL) was added to Pd/C (1.20 g, 10% weight of Pd on activated carbon), and MeOH (120 mL) was added to the suspension. The reaction mixture was stirred under H2 overnight (ca. 16 h). It was filtered through Celite washing with AcOEt (2×100 mL) and the solvent was concentrated off to give 2.54 g of the methylamine as pale brown oil. The crude was purified by flash chromatography on silica gel (10-20-60% MeOH/CH2Cl2), to yield 2.05 g of the title product (Rf=0.3 (AcOEt/MeOH/Et3N 20:3:2), pale yellow coloured oil, 74% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:19][NH:18][C:17](=[O:20])[CH2:16]2)=[CH:11][C:10]=1[O:21][CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[C:31]#[N:32].C1(O)C=CC=CC=1.N(C)(C)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:19][N:18]([C:28]3[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=3)[C:31]#[N:32])[C:17](=[O:20])[CH2:16]2)=[CH:11][C:10]=1[O:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1cccc(Br)c1
Reactant: O=C1CC(c2ccc(OCc3ccccc3)c(OC3CCCC3)c2)CN1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: CN(C)C
Solvent: ClCCl
Solvent: Oc1ccccc1
Product: N#Cc1cccc(N2CC(c3ccc(OCc4ccccc4)c(OC4CCCC4)c3)CC2=O)c1
Reaction time: 24 h
Yield: 74 %

Procedure:
A mixture of 4-(4-benzyloxy-3-cyclopentyloxyphenyl)pyrrolidin-2-one, 3-bromobenzonitrile, phenol (0.1 mmol), copper acetate (0.15 mmol), arylboronic acid (0.12 mmol), 4 Å Molecular Sieves (“MS”) (˜100 mg) and CH2Cl2 (1 mL) was created in a dry round bottom flask. (CH3)3N (0.22 mmol) was added, the flask was sealed, and the mixture was stirred for 24 h. The reaction mixture was then diluted with 10 mL of CH2Cl2 and filtered. The filtrate was washed with saturated NH4Cl, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel or preparative liquid chromatography-mass spectrometry LC-MS to give pure product. Yield: 74%.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[CH2:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.CC[O:29]C(C)=O>ClCCl.O>[CH2:12]([C:10]1[CH:11]=[C:3]([CH2:2][Cl:1])[CH:4]=[CH:5][C:6]=1[C:7]([OH:29])=[O:8])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: OCc1ccccc1
Reactant: CCOC(C)=O
Reactant: O=C(Cl)c1ccc(CCl)cc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(O)c1ccc(CCl)cc1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.2 h

Procedure:
A stirred suspension of 3.0 g (14 mmol) of 4-(bromomethyl)benzoic acid and 3.5 ml (41 mmol) of oxalyl chloride in 35 ml of dichloromethane was refluxed for 10 hours and cooled to room temperature. Evaporation afforded 4-(chloromethyl)benzoyl chloride as an oil which was used without purification. To a cooled (0° C.) solution of 2.6 g (14 mmol) of 4-(chloromethyl)benzoyl chloride and 2.0 g (18 mmol) of benzyl alcohol in 30 ml of dichloromethane was added 1.8 g (18 mmol) of triethylamine. The reaction was stirred at 0° C. for 0.2 hours, then at room temperature for an additional 1 hour and poured into 150 ml of EtOAc. The EtOAc layer was with three portions of water, dried over Na2SO4, filtered and evaporated. The crude product was flash chromatographed (5% EtOAc/hexanes) to give 0.7 g of product; m.p. 52°-54° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14].NCC(O)[CH2:19][OH:20].C(CN)O>>[OH:1][CH:2]([CH2:19][OH:20])[CH2:3][NH:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14]
Reactant: N#Cc1ccc(NCCO)c([N+](=O)[O-])c1
Reactant: NCC(O)CO
Solvent: NCCO
Product: N#Cc1ccc(NCC(O)CO)c([N+](=O)[O-])c1

Procedure:
Preparation is similar to the synthesis in (a) above, except that 3-amino-1,2-propanediol is used in lieu of monoethanolamine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27].O>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:6]=[C:5]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)c1c[nH]c2ccc(F)cc12
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1cn(S(C)(=O)=O)c2ccc(F)cc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl 5-fluoro-1H-indole-3-carboxylate (500 mg, 2.125 mmol) and triethylamine (1721 mg, 17.00 mmol) in THF (5 ml) was added methanesulfonyl chloride (0.658 ml, 8.50 mmol). The mixture was stirred at RT for 2 h. The reaction mixture was then poured into water and extracted twice with Et2O. The organic extracts were combined, filtered through MgSO4, concentrated, and purified by column chromatography (SiO2; EtOAc/hex) to afford the title compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:17])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.CCN(C(C)C)C(C)C.[CH3:27][CH:28]([N:30]1[C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=[N:31]1)[CH3:29].O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([NH:17][C:35]([C:34]2[N:30]([CH:28]([CH3:29])[CH3:27])[N:31]=[CH:32][CH:33]=2)=[O:36])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2
Reactant: Nc1cc(Br)cc2nn(C3CCCCO3)cc12
Reactant: CC(C)n1nccc1C(=O)Cl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)n1nccc1C(=O)Nc1cc(Br)cc2nn(C3CCCCO3)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.3 %

Procedure:
6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (2.25 g, 7.59 mmol) was dissolved in DCM (40 ml) and DIPEA (2.85 ml, 16.34 mmol) was added. 1-(1-methylethyl)-1H-pyrazole-5-carbonyl chloride (1.41 g, 8.17 mmol) in DCM (10 ml) was added and the mixture left to stir at room temperature overnight. Water (50 ml) was added and the mixture vigorously stirred. The DCM layer was passed through a hydrophobic frit and evaporated to dryness. The material was combined with that obtained from a previous smaller scale reaction carried out in an identical manner but starting with 6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (0.2 g, 0.675 mmol). The combined crude materials were purified by chromatography on silica using a 50 g cartridge and eluting progressively with DCM, then 1-4% methanol in DCM. Product containing fractions were combined and evaporated to dryness to afford the title compound (2.8 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH:10]([CH3:19])[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12]>C(N(CC)CC)C.C(O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[N:6]([CH:10]([CH3:19])[C:11](=[O:12])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1
Reactant: O=c1ncc(Cl)c[nH]1
Reactant: CC(Br)C(=O)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC(C(=O)c1ccccc1)n1cc(Cl)cnc1=O

Procedure:
A solution of 5-chloropyrimidin-2-one (394 mg) and α-bromopropiophenone (0.5 ml) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature for 2.75 hours. The solution was evaporated and the residue was triturated with water (50 ml) giving an oily solid. This was extracted with ethyl acetate (3×50 ml). The combined extracts were washed with brine (50 ml), dried (MgSO4) and evaporated to a gum. This was crystallised from acetone-petrol (b.p. 40°-60°) to give the title pyrimidinone (306 mg,); m.p. 125°-127°; λmaxEtOH 232 nm (ε 15400), 245 nm (ε 15480), 335 nm (ε 3970).
Reaction SMILES: C(O)(C(F)(F)F)=O.[C:8]([NH:11][C:12]1[CH:13]=[C:14]([CH:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][NH:27]C(=O)OC(C)(C)C)[CH2:20][CH2:19]2)[CH:15]=[CH:16][CH:17]=1)(=[O:10])[CH3:9].[OH-].[K+]>ClCCl>[NH2:27][CH2:26][CH2:25][CH2:24][N:21]1[CH2:22][CH2:23][CH:18]([C:14]2[CH:13]=[C:12]([NH:11][C:8](=[O:10])[CH3:9])[CH:17]=[CH:16][CH:15]=2)[CH2:19][CH2:20]1
Reactant: CC(=O)Nc1cccc(C2CCN(CCCNC(=O)OC(C)(C)C)CC2)c1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)Nc1cccc(C2CCN(CCCN)CC2)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 48.1 %

Procedure:
TFA (1.0 mL) was added to a solution of tert-butyl N-(3-{4-[3-(acetyl-amino)phenyl]piperidino}propyl)carbamate (340 mg) in dry dichloromethane (10 mL) and stirred at room temperature for 5 h. A 10% aqueous solution of KOH was added to the reaction mixture until pH >6 and then the dichloromethane was removed in vacuo. The aqueous layer was frozen and lyophilized, giving a solid which was then extracted with methanol. Removal of methanol gave the desired product (120 mg) as an oil. 1H NMR δ 8.56-8.46 (s, 1H), 7.43-7.30 (m, 2H), 7.23-7.16 (apparent t, 1H, J=7.5 Hz), 6.95-6.92 (m, 1H), 3.03-2.99 (m, 2H), 2.77-2.73 (t, 2H, J=6.6 Hz), 2.50-1.60 (m, 10 H), 2.13 (s, 3 H).
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5]([CH2:11][CH:12]=O)=[CH:4][CH:3]=1.Cl.[N:15]1([C:21](=[O:34])[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH:33]=[N:32][N:31]=[N:30]3)=[CH:25][CH:24]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.N1ON=C2C=C(CCN3CCN(C(=O)CC4C=CC(N5C=NN=N5)=CC=4)CC3)C=CC=12>>[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5]([CH2:11][CH2:12][N:18]2[CH2:17][CH2:16][N:15]([C:21](=[O:34])[CH2:22][C:23]3[CH:24]=[CH:25][C:26]([N:29]4[CH:33]=[N:32][N:31]=[N:30]4)=[CH:27][CH:28]=3)[CH2:20][CH2:19]2)=[CH:4][CH:3]=1
Reactant: Cc1c(CC=O)ccc(F)c1C#N
Reactant: O=C(Cc1ccc(-n2cnnn2)cc1)N1CCNCC1
Agent: Cl
Agent: O=C(Cc1ccc(-n2cnnn2)cc1)N1CCN(CCc2ccc3nonc3c2)CC1
Product: Cc1c(CCN2CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)CC2)ccc(F)c1C#N

Procedure:
6-Fluoro-2-methyl-3-[2-(4-{[4-(1H-tetrazol-1-yl)phenyl]acetyl}piperazin-1-yl)ethyl]benzonitrile was prepared from 6-fluoro-2-methyl-3-(2-oxoethyl)benzonitrile and 1-(piperazin-1-yl)-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone hydrochloride in an analogous fashion to that described for 1-{4-[2-(2,1,3-benzoxadiazol-5-yl)ethyl]piperazin-1-yl}-2-[4-(1H-tetrazol-1-yl)phenyl]ethanone (General Method C). 1H-NMR (400 MHz, CD3OD) δ 9.89 (s, 1H), 7.76˜7.78 (m, 2H), 7.51˜7.55 (m, 1H), 7.40˜7.42 (m, 2H), 7.21˜7.25 (m, 1H), 4.44˜4.45 (m, 1H), 4.16˜4.17 (m, 1H), 3.84 (s, 2H), 3.38˜3.56 (m, 2H), 2.98˜3.01 (m, 4H).
Reaction SMILES: [CH:1]1([N:4]([C@@H:20]([C:22]2[NH:31][C:30](=O)[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)[CH3:21])[C:5]([C@@H:7]2[O:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.[CH3:33][O:34][CH2:35][CH2:36][CH2:37]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH:1]1([N:4]([C@@H:20]([C:22]2[N:31]=[C:30]([CH2:37][CH2:36][CH2:35][O:34][CH3:33])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)[CH3:21])[C:5]([C@@H:7]2[O:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1
Reactant: C[C@H](c1nc2ccccc2c(=O)[nH]1)N(C(=O)[C@H]1CN(C(=O)OC(C)(C)C)CCO1)C1CC1
Reactant: COCCCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COCCCc1nc([C@@H](C)N(C(=O)[C@H]2CN(C(=O)OC(C)(C)C)CCO2)C2CC2)nc2ccccc12
Temperature: 25 °C
Reaction time: 19 h
Yield: 38.3 %

Procedure:
To a solution of tert-butyl (2R)-2-({cyclopropyl[(1R)-1-(4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]amino}carbonyl)morpholin-4-carboxylate (88 mg), 3-methoxy-1-propanol (36 mg) and triphenylphosphine (105 mg) in tetrahydrofuran (4 mL) was added dropwise diisopropyl azodicarboxylate (84 μL) under ice-cooling, and the mixture was stirred at room temperature for 19 hours. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1→1/2) to give tert-butyl (2R)-2-[(cyclopropyl{(1R)-1-[4-(3-methoxypropyl)quinazolin-2-yl]ethyl}amino)carbonyl]morpholin-4-carboxylate [Ex(168-1)] (38 mg) as a colorless oil.
Reaction SMILES: C(O[C:5](=[O:7])C)(=O)C.C(O)=O.[C:11]1([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[N:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O1CCCC1>[CH:5]([N:29]1[CH2:30][CH2:31][N:26]([C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:17]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:18]=2)[CH2:27][CH2:28]1)=[O:7]
Reactant: c1ccc(-n2nc(N3CCNCC3)c3ccccc32)cc1
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Solvent: O=CO
Product: O=CN1CCN(c2nn(-c3ccccc3)c3ccccc23)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 42 %

Procedure:
To a solution of 3.4 ml of acetic anhydride and 1.5 ml of formic acid heated at 55° C. for 1.5 hours and then cooled to ambient temperature was added, dropwise, a solution of 5.6 g of 1-phenyl-3-(1-piperazinyl)-1H-indazole in 20 ml of tetrahydrofuran. The reaction mixture was stirred at ambient temperature for 2 hours and then concentrated to an oil. Trituration of the oil with refluxing diethyl ether yielded a solid which was recrystallized from isopropanol (3×) to yield 2.6 g (42%) of 4-formyl-1-(1-phenyl-1H-indazol-3-yl)piperazine, m.p. 130°-132°.
Reaction SMILES: [CH2:1]([Sn:5]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:16][CH2:17][CH2:18][CH3:19])/[CH:6]=[CH:7]/[C:8]([CH3:15])([OH:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:2][CH2:3][CH3:4].N1C=CN=C1.Cl[Si:30]([CH3:33])([CH3:32])[CH3:31]>CN(C)C=O>[CH2:20]([Sn:5]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:1][CH2:2][CH2:3][CH3:4])/[CH:6]=[CH:7]/[C:8]([CH3:15])([O:14][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:21][CH2:22][CH3:23]
Reactant: CCCCCC(C)(O)/C=C/[Sn](CCCC)(CCCC)CCCC
Reactant: C[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CCCCCC(C)(/C=C/[Sn](CCCC)(CCCC)CCCC)O[Si](C)(C)C

Procedure:
The vinylstannane is treated with imidazole, and chlorotrimethylsilane in dimethylformamide by the procedure of Example 1 to provide (E)-1-tri-n-butylstannyl-3-methyl-3-trimethylsilyloxy-1-octene as an oil.
Reaction SMILES: COC1C=CC(NC2OC(C3C=CC4N=[C:21]([C:23]5[C:28]([CH3:29])=[CH:27][C:26]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[CH:25][C:24]=5[CH3:35])NC=4C=3)=NN=2)=CC=1.[CH2:37]([OH:40])[CH2:38][OH:39].[CH3:41]C1C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[CH3:41][O:34][C:32](=[O:33])[CH2:31][CH2:30][C:26]1[CH:25]=[C:24]([CH3:35])[C:23]([CH:21]2[O:40][CH2:37][CH2:38][O:39]2)=[C:28]([CH3:29])[CH:27]=1
Reactant: OCCO
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: COc1ccc(Nc2nnc(-c3ccc4nc(-c5c(C)cc(CCC(=O)O)cc5C)[nH]c4c3)o2)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)CCc1cc(C)c(C2OCCO2)c(C)c1

Procedure:
To a stirred solution of 3-(4-formyl-3,5-dimethylphenyl)-propionic acid methyl ester (prepared as described in Example 1-60, 2.2 g, 10 mmol) and ethane-1,2-diol (1.86 g, 30 mmol) in toluene (50 mL) was added p-TsOH.H2O (38 mg, 0.2 mmol) and the solution was refluxed using a Dean-Stark apparatus overnight. The solvent was removed under reduced pressure and the residue was purified by flash chromatography using heptane/EtOAc (5:1) as eluent to give 3-(4-[1,3]dioxolan-2-yl -3,5-dimethylphenyl)-propionic acid methyl ester as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:16][C:17]([CH3:32])([CH3:31])[CH2:18][CH2:19][O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[C@@H:10]([OH:15])[CH2:11][CH2:12][CH:13]=[CH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO[C:35](OC)([CH3:37])[CH3:36].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@@H:9]([CH2:16][C:17]([CH3:31])([CH3:32])[CH2:18][CH2:19][O:20][Si:21]([CH:25]([CH3:26])[CH3:27])([CH:22]([CH3:23])[CH3:24])[CH:28]([CH3:30])[CH3:29])[C@H:10]([CH2:11][CH2:12][CH:13]=[CH2:14])[O:15][C:35]1([CH3:37])[CH3:36])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(C)(C)OC
Reactant: C=CCC[C@H](O)[C@H](CC(C)(C)CCO[Si](C(C)C)(C(C)C)C(C)C)NC(=O)OC(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: C=CCC[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC(C)(C)CCO[Si](C(C)C)(C(C)C)C(C)C

Procedure:
1.80 g of 6(S)-tert-butoxycarbonylamino-8,8-dimethyl-5(S)-hydroxy-10-triisopropylsilyloxydec1-ene are stirred in 10 ml each of methylene chloride and dimethoxypropane with 50 mg of p-toluenesulfonic acid hydrate at room temperature for 2 h. After the mixture has been concentrated, the residue is purified over 250 g of silica gel with a 1:20 mixture of ethyl acetate and hexane as the mobile phase: Rf (1:20 mixture of ethyl acetate and hexane)=0.40.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]([C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:15][N:14](COCC[Si](C)(C)C)[C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]([C:17](=[O:22])[C:18]([CH3:20])([CH3:19])[CH3:21])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)C(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3cccc(N)c3)nc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3cccc(N)c3)nc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.1 %

Procedure:
To a microwave vial was added 0.032 gm (0.075 mM) 1-[2-(3-Amino-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one followed by 0.75 ml of 1M tetrabutylammonium fluoride in THF. The vial was sealed and placed in a 80° C. oil bath for two hours then stirred at room temperature overnight. The mixture was diluted with 10 ml ethyl acetate, rinsed (3×50 ml) water, dried over magnesium sulfate, filtered and concentrated on a rotary evaporator. Purification on a preparative silica gel thin layer chromatography plate (5/95 MeOH/CH2Cl2) gave 0.014 gm (64% yield) of 1-[2-(3-Amino-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one, M+1 295, M.P. 239-241° C.
Reaction SMILES: CC([Si](C)(C)[O:6][C:7]([C:10]#[C:11][CH2:12][C@H:13]([C:15]1[C@:32]2([CH3:33])[C@H:18]([C:19]3[C@H:29]([CH2:30][CH2:31]2)[C@:27]2([CH3:28])[C:22]([CH2:23][C@@H:24]([O:42][Si](C)(C)C(C)(C)C(C)C)[CH2:25][C@@H:26]2[O:34][Si](CC)(CC)CC)=[CH:21][CH:20]=3)[CH2:17][CH:16]=1)[CH3:14])([CH3:9])[CH3:8])(C)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-].CCOC(C)=O.O>O1CCCC1>[CH3:8][C:7]([OH:6])([C:10]#[C:11][CH2:12][C@H:13]([C:15]1[C@:32]2([CH3:33])[C@H:18]([C:19]3[C@H:29]([CH2:30][CH2:31]2)[C@:27]2([CH3:28])[C:22]([CH2:23][C@@H:24]([OH:42])[CH2:25][C@@H:26]2[OH:34])=[CH:21][CH:20]=3)[CH2:17][CH:16]=1)[CH3:14])[CH3:9]
Reactant: CC[Si](CC)(CC)O[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C(C)C)CC2=CC=C3[C@H](CC[C@]4(C)C([C@H](C)CC#CC(C)(C)O[Si](C)(C)C(C)(C)C)=CC[C@@H]34)[C@]21C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C[C@H](CC#CC(C)(C)O)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 40 h
Yield: 86.1 %

Procedure:
A mixture of 20.7 g (26.5 mmol) of (1α,3β)-[[25-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-[[dimethyl(1,1,2-trimethylpropyl)silyl]oxy]cholesta-5,7,16-trien-23-yn-1-yl]oxy]triethylsilane and 265 mL (265 mmol) of 1M Bu4NF in tetrahydrofuran was stirred at 30°-35° C. for 40 hr. After cooling to room temperature, 265 mL of EtOAc and 265 mL of water were added. The aqueous layer was extracted with 2×125 mL of EtOAc. The combined EtOAc solutions were concentrated to dryness. The residue was suspended in 130 mL of hexane and 130 mL of water, and the mixture was stirred for 30 min prior to filtration. The solid was washed with 130 mL of water and then with 130 mL of hexane. After being dried by suction, the solid was dissolved in 90 mL of hot methanol. After the solution was diluted with 45 mL of water and cooled to room temperature, the mixture was stored in a refrigerator overnight. The precipitate was filtered and washed with 100 mL of methanol-water (2:1). Drying at room temperature under high vacuum for 24 hr gave 9.37 g of (1α,3β)-cholesta-5,7,16-trien-23-yne-1,3,25-triol