Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]1[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]1)[CH:8]=[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:6]2=[O:24].[N:25]1[CH:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.C([BH3-])#N.[Na+].O>CO>[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]1[CH2:18][CH2:17][CH2:16][N:15]([CH2:31][C:28]3[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=3)[CH2:14]1)[CH:8]=[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:6]2=[O:24]
Reactant: O=Cc1ccncc1
Reactant: CCOC(=O)c1cn(C2CCCNC2)c2ccc(I)cc2c1=O
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCOC(=O)c1cn(C2CCCN(Cc3ccncc3)C2)c2ccc(I)cc2c1=O
Temperature: 23 °C
Reaction time: 16 h
Yield: 82.3 %

Procedure:
Ethyl 6-iodo-4-oxo-1-(piperidin-3-yl)-1,4-dihydroquinoline-3-carboxylate hydrochloride (Intermediate 132, 500 mg, 1.08 mmol) was suspended in methanol (15 mL) then 4-pyridinecarboxaldehyde (520 μl, 5.4 mmol) and sodium cyanoborohydride (612 mg, 9.7 mmol) were added. The reaction was stirred at 23° C. for 16 h. The volume of the reaction was reduced by half and water (25 mL) was added. The suspension was extracted with 2:1 ethyl acetate: tetrahydrofuran (3×, 10 mL). The organic phases were combined, dried over sodium sulfate, and the solvent was removed in vacuo. The residue was passed through a plug of silica gel (2 g) eluting with 10% methanol in dichloromethane to remove any remaining borohydride. The solid was then dried in a vacuum oven at 50° C. for 18 h to give 460 mg (82% yield) of ethyl 6-iodo-4-oxo-1-(1-(pyridin-4-ylmethyl)piperidin-3-yl)-1,4-dihydroquinoline-3-carboxylate as an off white solid.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([O:14][N:15]=[C:16]([NH2:25])[C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])=O)=[CH:7][CH:6]=1)([CH3:3])[CH3:2]>CN(C=O)C>[Cl:24][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([Cl:23])[C:17]=1[C:16]1[N:25]=[C:12]([CH2:11][C:8]2[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)[O:14][N:15]=1
Reactant: CC(C)Oc1ccc(CC(=O)ON=C(N)c2c(Cl)cccc2Cl)cc1
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc(Cc2nc(-c3c(Cl)cccc3Cl)no2)cc1

Procedure:
A solution of 102.5 g of N'-(4-isopropoxyphenylacetoxy)-2,6-dichlorobenzamidine in 500 ml of DMF was heated at 140° C. for 1.5 hours.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([OH:8])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:33][CH:34]1[CH2:39][CH2:38][N:37]([C:40]2[C:49]3[C:44](=[CH:45][C:46]([CH3:50])=[CH:47][CH:48]=3)[N:43]=[C:42]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=3[OH:57])[N:41]=2)[CH2:36][CH2:35]1.C(N(CC)CC)C>CN(C=O)C>[OH:57][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=1[C:42]1[N:41]=[C:40]([N:37]2[CH2:36][CH2:35][CH:34]([NH:33][C:6]([C@H:2]3[CH2:3][CH2:4][CH2:5][O:1]3)=[O:8])[CH2:39][CH2:38]2)[C:49]2[C:44](=[CH:45][C:46]([CH3:50])=[CH:47][CH:48]=2)[N:43]=1
Reactant: Cc1ccc2c(N3CCC(N)CC3)nc(-c3ccccc3O)nc2c1
Reactant: O=C(O)[C@H]1CCCO1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc2c(N3CCC(NC(=O)[C@H]4CCCO4)CC3)nc(-c3ccccc3O)nc2c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 42.2 %

Procedure:
(R)-Tetrahydrofuran-2-carboxylic acid (193 mg, 1.66 mmol) was dissolved in DMF (6 mL), followed by the addition of HATU (696 mg, 1.83 mmol). The mixture was then stirred for 15 min at room temperature under an N2 atmosphere. The 2-[4-(4-Amino-piperidin-1-yl)-7-methyl-quinazolin-2-yl]-phenol (556 mg, 1.66 mmol) was dissolved in DMF (8 mL) and added to the mixture, followed by triethylamine (336 mg, 0.463 mL, 3.32 mmol). After 30 min, theDMF was removed in vacuo and the crude product partitioned between water and ethyl acetate. The aqueous layer was separated, washed with ethyl acetate, and the combined organic layers dried over MgSO4, filtered, and concentrated to give crude product as an orange oil. Purification via silica gel chromatography (20% ethyl acetate/80% 1:1 CH2Cl2:hexane) gave pure (R)-Tetrahydro-furan-2-carboxylic acid {1-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperidin-4-yl}-amide (303 mg, 42%). 1H NMR (400 MHz, DMSO-d6) δ 8.44 (dd, J=8.2, 1.5 Hz, 1H), 7.90 (d, J=8.5 Hz, 1H), 7.75 (d, J=8.3 Hz, 1H), 7.67 (s, 1H), 7.40-7.36 (m, 2H), 6.97-6.93 (m, 2H), 4.48-4.45 (m, 2H), 4.20 (dd, J=8.2, 5.3 Hz, 1H), 4.06-3.96 (m, 1H), 3.88 (dd, J=14.3, 6.6 Hz, 1H), 3.74 (dd, J=14.5, 6.7 Hz, 1H), 3.43-3.32 (m, 2H), 2.51 (s, 3H), 2.16-2.07 (m, 1H),
Reaction SMILES: N#N.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[CH2:19]1[CH2:40][O:39][CH:38]2[CH:21]([CH2:22][C:23]3[C@:36]([CH:41]=[O:42])([CH2:37]2)[C@@H:35]2[C@H:26]([C@H:27]4[C@@:31]([CH2:33][CH2:34]2)([CH3:32])[CH:30]2[O:43][CH2:44][CH2:45][O:46][CH:29]2[CH2:28]4)[CH2:25][CH:24]=3)[O:20]1>C(=O)=O.CC(C)=O.O1CCCC1>[CH2:19]1[CH2:40][O:39][CH:38]2[CH:21]([CH2:22][C:23]3[C@:36]([CH:41]([CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15])[OH:42])([CH2:37]2)[C@@H:35]2[C@H:26]([C@H:27]4[C@@:31]([CH2:33][CH2:34]2)([CH3:32])[CH:30]2[O:43][CH2:44][CH2:45][O:46][CH:29]2[CH2:28]4)[CH2:25][CH:24]=3)[O:20]1
Reactant: CCOC(C)=O
Reactant: C[C@]12CC[C@H]3[C@@H](CC=C4CC5OCCOC5C[C@@]43C=O)[C@@H]1CC1OCCOC12
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: N#N
Agent: O=C=O
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)CC(O)[C@]12CC3OCCOC3CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C3OCCOC3C[C@@H]12
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A 50 mL 2-neck flask equipped with a rubber septum, magnetic stirring bar and N2 inlet was charged with lithium bis(trimethylsilyl)amide (12.9 mL of 1.0M solution, 12.9 mmol). The solution was cooled to -78° C. under N2 in dry ice-acetone bath and anhydrous ethyl acetate (1.2 mL, 12.9 mmol) was added dropwise from a syringe. The reaction was stirred at -78° C. for 30 minutes and then a solution of 3,17-bis(ethylenedioxy)-5-androsten-19-al (1 g, 2.58 mmol) (Lovett, J. A. et al., 1984, J. Med. Chem. 27:734-740) in anhydrous tetrahydrofuran (15 mL) was added dropwise to the solution of the enolate. After completion of the addition, the reaction was stirred for an additional 1.5 hours in the dry ice-acetone bath under nitrogen. The reaction was then quenched with the addition of saturated ammonium chloride solution (~ 30 mL) and the resulting suspension was extracted three times with ethyl acetate (3×25 mL). The combined ethyl acetate extract was washed once with brine (~ 30 mL) and was then dried over magnesium sulfate. After filtration, the solvent was removed under reduced pressure to yield an oil which was used as such in the next reaction: yield 1.67 g (crude); mass spectrum (chemical ionization) m/z 477 (M+H+).
Reaction SMILES: C(OC([NH:8][C:9]1[O:10][C:11]2[CH:19]=[C:18]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:17]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:16][C:12]=2[C:13](=[O:15])[CH:14]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[NH2:8][C:9]1[O:10][C:11]2[CH:19]=[C:18]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:17]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:16][C:12]=2[C:13](=[O:15])[CH:14]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(=O)c2cc(Oc3ccccc3)c(NS(C)(=O)=O)cc2o1
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)Nc1cc2oc(N)cc(=O)c2cc1Oc1ccccc1

Procedure:
2-tert-Butoxycarbonylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one was reacted with trifluoroacetic acid to obtain 2-amino-7-methylsulfonylamino- 6-phenoxy-4H-1-benzopyran-4-one.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.[N:19]1([C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH:34]=[CH:33][NH:32][C:31]3=[O:35])=[CH:26][CH:25]=2)[CH:23]=[CH:22][N:21]=[CH:20]1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:10])([CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C@H:11]([N:32]1[CH:33]=[CH:34][N:30]([C:27]2[CH:28]=[CH:29][C:24]([N:19]3[CH:23]=[CH:22][N:21]=[CH:20]3)=[CH:25][CH:26]=2)[C:31]1=[O:35])[CH3:12]
Reactant: O=c1[nH]ccn1-c1ccc(-n2ccnc2)cc1
Reactant: C[C@@H]1O[C@@]1(Cn1cncn1)c1ccc(F)cc1F
Product: C[C@@H](n1ccn(-c2ccc(-n3ccnc3)cc2)c1=O)[C@](O)(Cn1cncn1)c1ccc(F)cc1F

Procedure:
(2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane was reacted with 1-[4-(1H-1-imidazolyl)phenyl]-2(1H,3H)-imidazolone in the same manner as in Working Example 11 to give 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-imidazolyl)phenyl]-2(1H,3H)-imidazolone (Compound 23).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:23])[C:9]([C:15]2[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:24])[CH:3]=1.[C:25]([CH2:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)#[N:26]>>[Cl:24][C:4]1[CH:3]=[C:2]([C:31]2[CH:32]=[CH:33][C:28]([CH2:27][C:25]#[N:26])=[CH:29][CH:30]=2)[CH:7]=[CH:6][C:5]=1[CH:8]([CH3:23])[C:9]([OH:14])([C:15]1[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=1)[C:10]([F:13])([F:12])[F:11]
Reactant: N#CCc1ccc(B(O)O)cc1
Reactant: COc1ccc(C(O)(C(C)c2ccc(Br)cc2Cl)C(F)(F)F)cn1
Product: COc1ccc(C(O)(C(C)c2ccc(-c3ccc(CC#N)cc3)cc2Cl)C(F)(F)F)cn1

Procedure:
In analogy to Example 150, step 2, 3-(4-bromo-2-chloro-phenyl)-1,1,1-trifluoro-2-(6-methoxy-pyridin-3-yl)-butan-2-ol (Example 175, step 3) was reacted with 4-cyanomethylphenylboronic acid to give the title compound as a colorless foam. MS (m/e)=461.3 [M+H+]
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:18]=[C:17]([OH:19])[C:16]([OH:20])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:8].[N+:21]([O-])([O-:23])=[O:22].[K+]>CS(O)(=O)=O>[Cl:1][C:2]1[C:3]2[C:18]([N+:21]([O-:23])=[O:22])=[C:17]([OH:19])[C:16]([OH:20])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]([N:9]1[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1)=[O:8]
Reactant: O=C(c1sc2cc(O)c(O)cc2c1Cl)N1CCOCC1
Reactant: O=[N+]([O-])[O-]
Agent: CS(=O)(=O)O
Agent: [K+]
Product: O=C(c1sc2cc(O)c(O)c([N+](=O)[O-])c2c1Cl)N1CCOCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
(3-Chloro-5,6-dihydroxy-benzo[b]thiophen-2-yl)-morpholin-4-yl-methanone (2.0 g) from Example 28 was slurried in methanesulfonic acid (40 ml) and then potassium nitrate (0.64 g) was gradually added. The reaction mixture was stirred at room temperature and after 15 min it was poured into ice water (100 ml). The solid was filtered, washed with water (50 ml) and dried in vacuum. The resultant solid was dissolved in DMF (6.2 ml) and then ethanol (18.4 ml) was added. The product was filtered and washed with methanol (15 ml).
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:4]2[N:5]([CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[N:11]=2)[CH:6]=[CH:7][CH:8]=1.[K+].[Br-]>>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([C:10]2[N:11]=[C:4]3[C:3]([CH:2]=[O:1])=[CH:8][CH:7]=[CH:6][N:5]3[CH:9]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: COc1cccc(-c2cn3cccc(CO)c3n2)c1
Agent: [Br-]
Agent: [K+]
Product: COc1cccc(-c2cn3cccc(C=O)c3n2)c1
Yield: 40 %

Procedure:
From 3d, reaction time 8 h (yield: 40%); mp 71-73° C.; IR (KBr) 1691, 1364 cm−1; 1H NMR (400 MHz, CDCl3) δ 3.90 (s, 3H), 6.89 (m, 2H), 7.34 (t, 1H, J=7 Hz), 7.53 (d, 1H, J=7 Hz), 7.58 (s, 1H), 7.76 (d, 1H, J=7 Hz), 7.90 (s, 1H), 8.29 (d, 1H, J=7 Hz); 13C NMR (100 MHz, CDCl3) δ 55.4, 108.7, 111.5, 111.8, 114.4, 118.7, 123.7, 125.6, 129.8, 130.3, 134.5, 144.5, 147.0, 160.1, 189.1. MS m/z 252 (M+, 64), 224 (100), 193 (42), 181 (18).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12][C:13]2[C:21]3[C:16](=[C:17]([F:23])[C:18]([Cl:22])=[CH:19][CH:20]=3)[NH:15][C:14]=2[CH3:24])[N:7]=1)[CH3:2].Br[C:27]1[CH:28]=[N:29][N:30]([CH2:32][CH3:33])[CH:31]=1>>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12][C:13]2[C:21]3[C:16](=[C:17]([F:23])[C:18]([Cl:22])=[CH:19][CH:20]=3)[N:15]([C:27]3[CH:28]=[N:29][N:30]([CH2:32][CH3:33])[CH:31]=3)[C:14]=2[CH3:24])[N:7]=1)[CH3:2]
Reactant: CCn1cc(Br)cn1
Reactant: CCOC(=O)Cc1cccc(Sc2c(C)[nH]c3c(F)c(Cl)ccc23)n1
Product: CCOC(=O)Cc1cccc(Sc2c(C)n(-c3cnn(CC)c3)c3c(F)c(Cl)ccc23)n1

Procedure:
Prepared according to the procedure described in Example 9, Step 4, using the following starting materials: [6-(6-chloro-7-fluoro-2-methyl-1H-indol-3-ylsulfanyl)-pyridin-2-yl]-acetic acid ethyl ester and 4-bromo-1-ethyl-1H-pyrazole.
Reaction SMILES: [NH2:1][C@@H:2]([CH3:12])[CH2:3][CH2:4][CH2:5][N:6]([CH2:10][CH3:11])[CH2:7][CH2:8][OH:9].Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1.NC(C)CCCN(CC)CCO>>[CH3:11][CH2:10][N:6]([CH2:7][CH2:8][OH:9])[CH2:5][CH2:4][CH2:3][C@@H:2]([NH:1][C:14]1[CH:15]=[CH:16][N:17]=[C:18]2[C:23]=1[CH:22]=[CH:21][C:20]([Cl:24])=[CH:19]2)[CH3:12]
Reactant: CCN(CCO)CCC[C@H](C)N
Reactant: Clc1ccc2c(Cl)ccnc2c1
Agent: CCN(CCO)CCCC(C)N
Product: CCN(CCO)CCC[C@H](C)Nc1ccnc2cc(Cl)ccc12

Procedure:
(S)-(+)-Hydroxychloroquine was prepared by condensing (S)-(+)-2-[(4-aminopentyl)ethylamino]ethanol with 4,7-dichloroquinoline. The latter compound is known. The (S)-(+)-2-[(4-aminopentyl)ethylamino]ethanol was prepared by resolving known racemic 2-[(4-aminopentyl)ethylamino]-ethanol by forming a salt thereof with known (S)-(+)-mandelic acid and separating the (S)-(+)-mandelic acid salts of the two enantiomers by crystallization.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:5][NH:6][CH:7]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:16][C:17]3[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:18]=3[C:19]([O:21]C)=[O:20])[CH:13]=2)[CH2:8]1.[OH-].[Na+].O>C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:5][NH:6][CH:7]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:16][C:17]3[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:18]=3[C:19]([OH:21])=[O:20])[CH:13]=2)[CH2:8]1
Reactant: COC(=O)c1cc([N+](=O)[O-])ccc1Nc1ccc2c(c1)CC(NCc1ccc(Cl)c(Cl)c1)C2
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1cc([N+](=O)[O-])ccc1Nc1ccc2c(c1)CC(NCc1ccc(Cl)c(Cl)c1)C2
Temperature: 25 °C
Reaction time: 18 h
Yield: 60.2 %

Procedure:
The methyl benzoate (0.65 g) was dissolved in 10 mL 1:1 THF/MeOH, and this solution was treated with 2 mL 50% NaOH and 1 mL water and stirred at room temperature for 18 hours. When the starting material was no longer observed by mass spec, the mixture was concentrated, the solids were dissolved in ethyl acetate/water 1:1. The layers were separated, and the aqueous layer was extracted with 2×20 mL ethyl acetate. The organic layers were combined and washed with 10 mL 50% saturated NaCl, dried over MgSO4/Na2SO4, filtered, and concentrated. The residual oil was purified by column chromatography (MPLC, silica, gradient 98:2 to 80:20)(CH2Cl2/MeOH+1% NH4OH). Fractions containing the desired product were combined, concentrated, and dried in vacuo overnight to give 2-[2-(3,4-dichlorobenzylamino)-indan-5-ylamino]-5-nitro-benzoic acid (0.38 g, 60% yield). MS (APCI) m/z 470.0 (M+−1). CHN for (C23H19Cl2N3O4·CH2Cl2) calc: C, 55.58, H, 3.94, N, 8.31; found: C, 55.25, H, 3.88, N, 8.32.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C@:15]([OH:32])([CH2:16][C@@H:17]([O:28][C:29](=[O:31])[CH3:30])[CH2:18][C@@H:19]2[OH:27])[CH:14]=[CH:13]3)[CH2:10][CH2:9]1)[CH3:7].COC(OC)C(C)[C@@H]1[C@]2(C)[C@H]([C@H:41]3[C@H:51](CC2)[C@:49]2(C)[C@:44](O)(C[C@@H](O)C[C@@H:48]2[OH:56])[CH:43]=[CH:42]3)CC1>>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C@:15]([OH:32])([CH2:16][C@@H:17]([O:28][C:29](=[O:31])[CH3:30])[CH2:18][C@@H:19]2[O:27][C:48](=[O:56])[C:49]2[CH:51]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:14]=[CH:13]3)[CH2:10][CH2:9]1)[CH3:7]
Reactant: CC(=O)O[C@H]1C[C@H](O)[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](C(C)C5OCCO5)CC[C@H]4[C@@H]3C=C[C@@]2(O)C1
Reactant: COC(OC)C(C)[C@H]1CC[C@H]2[C@@H]3C=C[C@@]4(O)C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Product: CC(=O)O[C@H]1C[C@H](OC(=O)c2ccccc2)[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](C(C)C5OCCO5)CC[C@H]4[C@@H]3C=C[C@@]2(O)C1
Yield: 92.8 %

Procedure:
The reaction and workup procedures of Example 105 were repeated except that 350 mg of 20-(1,3-dioxolan-2-yl)-3β-acetoxypregn-6-ene-1α,5α-diol was used in lieu of 400 mg of 21,21-dimethoxy-20-methylpregn-6-ene-1α,3β,5α-triol to give 400 mg of 20-(1,3-dioxolan-2-yl)-3β-acetoxy-1α-benzoyloxypregn-6-en-5α-ol showing the following physical properties.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9](=O)[CH2:8][CH2:7][CH2:6][C:5]2=1.[CH3:16][C@@H:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)=O.C(N(CC)CC)C>C1(C)C=CC=CC=1.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C@H:9]([NH:24][C@@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH3:16])[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: O=C1CCCc2c1[nH]c1ccc(Br)cc21
Reactant: C[C@@H](N)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@@H](N[C@@H]1CCCc2c1[nH]c1ccc(Br)cc21)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 68.4 %

Procedure:
A mixture of 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one (50 mg, 0.19 mmol), (R)-α-methylbenzylamine (23 mg, 0.19 mmol), and p-toluenesulfonic acid (5 mg) in toluene (15 mL) were refluxed with a Dean-Stark trap for 16 hours. The mixture was concentrated and the residue dried under high vacuum. The residue was dissolved in dichloromethane (3 mL) before formic acid (0.036 mL, 0.95 mmol), triethylamine (0.052 mL, 0.38 mmol), and (S)-RuCl[(1R,2R)-p-TsNCH(C6He)CH(C6H6)NH2](η-benzene) (16 mg, 0.038 mmol) were added and stirred for one hour at room temperature. (S)-RuCl[(1R,2R)-p-TsNCH(C6H6)CH(C6H6)NH2](η-benzene) was prepared as described in Journal of American Chemical Society 1996, 118, 2521-2522, and references therein, incorporated herein by reference with regard to such synthesis. The mixture was diluted with dichloromethane (10 mL) and washed with saturated sodium bicarbonate (10 mL). The organic phase was applied directly to a silica gel chromatography column and was eluted with 5% ethyl acetate in dichloromethane. Appropriate fractions were concentrated to yield 48 mg (68%, 90% de) of (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine. 1H NMR (DMSO-d6): δ 10.84 (s, 1H), 7.47 (m, 3H), 7.32 (m, 3H), 7.22 (t, 1H), 7.12 (d, 1H), 4.10 (m, 1H), 3.78 (m, 1H), 2.50 (m under DMSO, 2H), 2.16 (bs, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 1.59 (m, 1H), 1.49 (m, 1H), 1.31 (d, 3H); MS m/z 368 (M−1). (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine (48 mg, 90% de) was dissolved in ethyl ether (2 mL) before 1 M HCl in ether (2 mL) was added dropwise. The resulting precipitate was collected by filtration to yield 36 mg of a yellow solid. The solid was dissolved in hot methanol (2 mL). The solution was allowed to cool and ethyl ether added dropwise until the solution became cloudy. Crystals precipitated and were collected by filtration to yield 16 mg (30%, 100% de) of (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride. 1H NMR (DMSO-d6): δ 11.66 (s, 1H), 9.86 (bs, 1H), 9.29 (m, 1H), 7.76 (d, 2H), 7.66 (s, 1H), 7.36-7.48 (m, 4H), 7.24 (d, 1H), 4.73 (m, 1H), 4.55 (m, 1H), 2.63 (m, 2H), 2.09 (m, 1H), 1.96 (m, 2H), 1.79 (m, 1H), 1.67 (d, 3H). MS m/z 367, 369 (M−1).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:39])[C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[C:23]4[C:29]([C:30]5[CH:35]=[CH:34][C:33]([C:36](=[O:38])[NH2:37])=[CH:32][CH:31]=5)=[CH:28][NH:27][C:24]4=[N:25][CH:26]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:40]>CO.O1CCOCC1>[ClH:40].[N:11]1([C:14]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[C:23]4[C:29]([C:30]5[CH:31]=[CH:32][C:33]([C:36]([NH2:37])=[O:38])=[CH:34][CH:35]=5)=[CH:28][NH:27][C:24]4=[N:25][CH:26]=3)=[CH:17][CH:16]=2)=[O:39])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2ccc(-c3cnc4[nH]cc(-c5ccc(C(N)=O)cc5)c4c3)cc2)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: NC(=O)c1ccc(-c2c[nH]c3ncc(-c4ccc(C(=O)N5CCNCC5)cc4)cc23)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 116 %

Procedure:
A solution of 4-{4-[3-(4-carbamoyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoyl}-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.19 mmol) in MeOH (3 ml) was treated with 4 N HCl in dioxane (2.5 ml) and stirred at room temperature for 1 hr. The mixture was evaporated, taken up in MeOH and evaporated again. This was repeated twice to give 102 mg (116%) of the title compound. MS ESI (m/z): MS ESI (m/z): 426.4 (M+1)+, calc. 425.
Reaction SMILES: NC1C=C(C2CCN(C(OC(C)(C)C)=O)CC=2)C=CC=1.C([O-])([O-])=O.[Na+].[Na+].FC(F)(F)S(O[C:33]1[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:37][CH:38]=1)(=O)=O.[N+:48]([C:51]1[CH:52]=[C:53](B(O)O)[CH:54]=[CH:55][CH:56]=1)([O-:50])=[O:49].[Cl-].[Li+]>C(COC)OC>[N+:48]([C:51]1[CH:56]=[C:55]([C:33]2[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:37][CH:38]=2)[CH:54]=[CH:53][CH:52]=1)([O-:50])=[O:49]
Reactant: CC(C)(C)OC(=O)N1CC=C(OS(=O)(=O)C(F)(F)F)CC1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Agent: CC(C)(C)OC(=O)N1CC=C(c2cccc(N)c2)CC1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1CC=C(c2cccc([N+](=O)[O-])c2)CC1
Yield: 82.7 %

Procedure:
According to the procedure used for the synthesis of tert-butyl 4-[3-(amino)phenyl]-1,2,3,6-tetrahydro-1-pyridinecarboxylate, a mixture of 2 M aqueous Na2CO3 solution (2.2 mL), tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-1,2,3,6-tetrahydro-1-pyridine-carboxylate (0.500 g, 1.51 mmol), 3-nitrophenylboronic acid (0.353 g, 2.11 mmol), lithium chloride (0.191 g, 4.50 mmol) and tetrakistriphenylphosphine palladium (0) (0.080 g, 0.075 mmol) in dimethoxyethane (5 mL) afforded 0.380 g of the desired product.
Reaction SMILES: C(OC([NH:11][CH2:12][CH2:13][CH2:14][C@H:15]1[NH:20][C:19](=[O:21])[C@@H:18]([CH2:22][C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([CH3:32])[CH:24]=2)[NH:17][C:16]1=[O:33])=O)C1C=CC=CC=1>C(O)C>[NH2:11][CH2:12][CH2:13][CH2:14][C@H:15]1[NH:20][C:19](=[O:21])[C@@H:18]([CH2:22][C:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]([CH3:32])[CH:24]=2)[NH:17][C:16]1=[O:33]
Reactant: Cn1cc(C[C@H]2NC(=O)[C@@H](CCCNC(=O)OCc3ccccc3)NC2=O)c2ccccc21
Solvent: CCO
Product: Cn1cc(C[C@H]2NC(=O)[C@@H](CCCN)NC2=O)c2ccccc21

Procedure:
A solution of (3R,6R)-3-(3-benzyloxycarbonylaminopropyl)-6-(1-methylindol-3-ylmethyl)piperazine-2,5-dione (1.2 g) in ethanol (240 ml) containing 10% paradium on charcoal (0.6 g) was hydrogenated at ambient temperature and atmospheric pressure. After catalyst was filtered off and solvent was evaporated, crude solid was taken up with ethanol, and dried in vacuo to give (3R,6R)-3-(3-aminopropyl)-6-(1-methylindol-3-ylmethyl)piperazine-2,5-dione.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]([CH2:20][C:21]([OH:23])=O)[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:12])=[O:11].[CH2:24]([NH:26][CH2:27][CH2:28][C:29]#[N:30])[CH3:25]>>[C:29]([CH2:28][CH2:27][N:26]([CH2:24][CH3:25])[C:21](=[O:23])[CH2:20][N:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])[S:10]([C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:12])=[O:11])#[N:30]
Reactant: CCNCCC#N
Reactant: COc1ccccc1N(CC(=O)O)S(=O)(=O)c1ccccc1C
Product: CCN(CCC#N)C(=O)CN(c1ccccc1OC)S(=O)(=O)c1ccccc1C

Procedure:
prepared by reaction of [(2-methoxy-phenyl)-(toluene-2-sulfonyl)-amino]-acetic acid with 3-ethylamino-propionitrile