original_index
int64
2
1.77M
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
date_of_experiment
timestamp[ns]date
extracted_from_file
stringclasses
489 values
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
stringlengths
1
208
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
stringlengths
1
285
rxn_str
stringlengths
87
6.12k
rxn_time
float64
0
2.16k
solvent_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
stringclasses
330 values
temperature
float64
-230
30.1k
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
agent_003
null
agent_004
null
agent_005
null
agent_006
null
agent_007
null
agent_008
null
agent_009
null
agent_010
null
agent_011
null
agent_012
null
agent_013
null
agent_014
null
agent_015
null
agent_016
null
solvent_003
null
solvent_004
null
solvent_005
null
solvent_006
null
solvent_007
null
solvent_008
null
solvent_009
null
solvent_010
null
212,457
null
null
null
null
ord_dataset-e6e5ffd5405c481d8061087049155f9f
1990-01-01T00:07:00
true
Ethyl 2-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropylthio]benzimidazole-5-carboxylate was prepared in a similar manner to Example 2 with 3-(4-acetyl-3-hydroxy-2-propylphenoxy)-1,2-epoxypropane (1.91 g) and ethyl 2-mercaptobenzimidazole-5-carboxylate (1.70 g). 2.10 g (58.1%) of the esters was obtained as a yellow oil. This ester (2.10 g) was converted to the title compound (870 mg. 44.1%) as pale brown crystals in the same manner as Example 2, mp 133-135° C.
CCCc1c(OCC(O)CSc2nc3ccc(C(=O)OCC)cc3[nH]2)ccc(C(C)=O)c1O
null
CCOC(=O)c1ccc2nc(S)[nH]c2c1
CCCc1c(OCC2CO2)ccc(C(C)=O)c1O
null
[C:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][CH:10]2[O:12][CH2:11]2)=[C:6]([CH2:15][CH2:16][CH3:17])[C:5]=1[OH:18])(=[O:3])[CH3:2].[SH:19][C:20]1[NH:21][C:22]2[CH:28]=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:26]=[CH:25][C:23]=2[N:24]=1>>[C:1]([C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][CH:10]([OH:12])[CH2:11][S:19][C:20]2[NH:21][C:22]3[CH:28]=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:26]=[CH:25][C:23]=3[N:24]=2)=[C:6]([CH2:15][CH2:16][CH3:17])[C:5]=1[OH:18])(=[O:3])[CH3:2]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
479,344
null
null
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
Following the procedure of Example 97, the reaction of 1,2,4-triazole with 2-chloro-6-ethyl-4-(3,4-ethylendioxybenzylamino)-thieno-[2,3-d]-pyrimidine gives 2-(1,2,4-triazol-1-yl)-6-ethyl-4-(3,4-ethylendioxybenzylamino)-thieno-[2,3-d]-pyrimidine.
CCc1cc2c(NCc3ccc4c(c3)OCCO4)nc(-n3cncn3)nc2s1
null
CCc1cc2c(NCc3ccc4c(c3)OCCO4)nc(Cl)nc2s1
c1nc[nH]n1
null
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.Cl[C:7]1[N:8]=[C:9]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]3[O:26][CH2:27][CH2:28][O:29][C:22]=3[CH:21]=2)[C:10]2[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]4[O:26][CH2:27][CH2:28][O:29][C:22]=4[CH:21]=3)[C:10]3[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=3[N:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,582,282
CC(C)[N-]C(C)C
[Li+]
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
To a solution of 2,4-difluoro-1-methoxybenzene (156 mg) in tetrahydrofuran (5 mL) at −78° C. is added a 2M solution of lithium diisopropylamide in THF (540 μL). After stirring for 45 min a solution of 1-(2-trimethylsilylethoxymethyl)-1H-benzimidazole-2-carbaldehyde (which can be prepared according to US2003/220341 or U.S. Pat. No. 6,476,041 for example) (300 mg) in tetrahydrofuran (5 mL) is added at −78° C. and the reaction mixture allowed to warm to room temperature. After hydrolysis with aqueous saturated ammonium chloride and extraction with ethyl acetate, the organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol from 100/0 to 95/5) to afford (2,6-difluoro-3-methoxyphenyl)[1-(2-trimethylsilylethoxymethyl)-1H-benzimidazol-2-yl]methanol.
COc1ccc(F)c(C(O)c2nc3ccccc3n2COCC[Si](C)(C)C)c1F
null
COc1ccc(F)cc1F
C[Si](C)(C)CCOCn1c(C=O)nc2ccccc21
null
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][CH3:10].C([N-]C(C)C)(C)C.[Li+].[CH3:19][Si:20]([CH3:37])([CH3:36])[CH2:21][CH2:22][O:23][CH2:24][N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[CH:34]=[O:35]>O1CCCC1>[F:1][C:2]1[C:3]([O:9][CH3:10])=[CH:4][CH:5]=[C:6]([F:8])[C:7]=1[CH:34]([C:26]1[N:25]([CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH3:36])([CH3:37])[CH3:19])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=1)[OH:35]
null
C1CCOC1
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
832,525
C[Si](C)(C)Cl
null
null
null
ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f
2008-01-01T00:07:00
true
Combine 2-nitro-meta-xylene (5 mL, 0.037 mol), N,N-dimethylformamide dimethylacetal (5.4 mL, 1.1 eq) and N,N-dimethylformamide (60 mL) in a flask and reflux under nitrogen for 2 days. Let cool to room temperature then concentrate to approximately one-half volume. Add methanol (40 mL) and trimethylsilylchloride (6.6 mL, 1.4 eq). Reflux overnight. Dilute with ethyl acetate after cooling to room temperature then extract with saturated sodium bicarbonate followed by brine. Dry over magnesium sulfate, filter and concentrate. Purification by column chromatography (9:1 Hexanes:ethyl acetate) gives 1.15 g (14%) product as a light yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 2.23 (s, 3H), 2.80 (d, J=5.36 Hz, 2H), 3.19 (s, 6H), 4.45 (m, 1H), 7.32 (m, 2H), 7.42 (m, 1H).
COC(Cc1cccc(C)c1[N+](=O)[O-])OC
null
Cc1cccc(C)c1[N+](=O)[O-]
COC(OC)N(C)C
null
[N+:1]([C:4]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH3:11])([O-:3])=[O:2].[CH3:12][O:13][CH:14]([O:18][CH3:19])N(C)C.CN(C)C=O.C[Si](Cl)(C)C>C(OCC)(=O)C.CO>[CH3:12][O:13][CH:14]([O:18][CH3:19])[CH2:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([CH3:10])[C:4]=1[N+:1]([O-:3])=[O:2]
null
CN(C)C=O
CO
CCOC(C)=O
25
null
14
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,297,256
O=[Pt]=O
null
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
3-[2-[5-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]ethyl]phenylmethyl azide is dissolved in ethanol, and a catalytic amount of PtO2 is added. The reaction flask is attached to a H2 balloon by way of a three-way stopcock, and the atmosphere is exchanged. The mixture is stirred at room temperature. The reaction is followed by TLC and terminated by replacing the atmosphere with N2 when the starting material has disappeared. The catalyst is removed by centrifugation or filtration over a filter membrane. The solution is evaporated and the residue used directly in the following step. If desired, the product can be purified by CC on silica gel eluting with CH2Cl2/methanol/Et3N or CH2Cl2/methanol/conc. aqueous NH3, or on deactivated basic alumina with CH2Cl2/methanol.
CC(C)(C)OC(=O)N1CC[C@H]1COc1cncc(CCc2cccc(CN)c2)c1
null
CC(C)(C)OC(=O)N1CC[C@H]1COc1cncc(CCc2cccc(CN=[N+]=[N-])c2)c1
null
null
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][N:29]=[N+]=[N-])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.O=[Pt]=O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][NH2:29])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
null
CCO
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,695,671
null
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
Reaction of 3-[6-amino-5-(pyridin-4-ylcarbamoyl)-pyridin-3-yl]-benzoic acid with ammonia gives “A99”; method 2: HPLC/MS: 1.64 min, [M+H]=334.
NC(=O)c1cccc(-c2cnc(N)c(C(=O)Nc3ccncc3)c2)c1
null
Nc1ncc(-c2cccc(C(=O)O)c2)cc1C(=O)Nc1ccncc1
N
null
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)=[CH:4][C:3]=1[C:17](=[O:25])[NH:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1.[NH3:26]>>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:10]([C:11](=[O:13])[NH2:26])[CH:9]=2)=[CH:4][C:3]=1[C:17]([NH:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1)=[O:25]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
116,373
null
null
null
null
ord_dataset-19041548671f410397ce7f00536a9be3
1984-01-01T00:04:00
true
To a solution of the above 1-methyl-3-methylthiomethyl-4-quinolone (4.86 g.) in dichloromethane (220 ml.) at -20° was added a solution of 3-chloroperbenzoic acid (85%, 4.86 g.) in dichloromethane (220 ml.) during 1 hour. The solution was allowed to warm to room temperature and extracted with saturated aqueous sodium bicarbonate until free of per-acid. The organic phase was dried over anhydrous magnesium sulphate and evaporated to give a solid product. The product was crystallised from acetone to give the novel 1-methyl-3-methylsulphinylmethyl-4-quinolone, m.p. 93°-95°.
Cn1cc(CS(C)=O)c(=O)c2ccccc21
null
O=C(OO)c1cccc(Cl)c1
CSCc1cn(C)c2ccccc2c1=O
null
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[C:4]([CH2:13][S:14][CH3:15])=[CH:3]1.ClC1C=CC=C(C(OO)=[O:24])C=1>ClCCl>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[C:4]([CH2:13][S:14]([CH3:15])=[O:24])=[CH:3]1
null
ClCCl
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
46,990
O=C([O-])[O-]
[K+]
null
null
ord_dataset-6d529f04a1724b5d85dcc290cf4c38bb
1978-01-01T00:10:00
true
1.07 g of potassium carbonate and 1.3 g of ethyl bromoacetate were added to a solution of 1.6 g of the product of Step A in 50 ml of methyl ethyl ketone and the mixture was refluxed for an hour and was cooled to 30° C. The mixture was filtered and the filtrate was evaporated to dryness. The residue was taken up in ethyl acetate and the solution was washed with water, dried and evaporated to dryness to obtain 2.3 g of ethyl (2-ethoxycarbonyl-5-chloro-3-thienyl)-oxyacetate.
CCOC(=O)COc1cc(Cl)sc1C(=O)OCC
null
CCOC(=O)c1sc(Cl)cc1O
CCOC(=O)CBr
null
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[CH2:14]([O:16][C:17]([C:19]1[S:20][C:21]([Cl:25])=[CH:22][C:23]=1[OH:24])=[O:18])[CH3:15]>C(C(C)=O)C>[CH2:14]([O:16][C:17]([C:19]1[S:20][C:21]([Cl:25])=[CH:22][C:23]=1[O:24][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:18])[CH3:15]
null
CCC(C)=O
null
null
30
null
101.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,381,749
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
null
ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81
2013-01-01T00:12:00
true
A solution 3-(2-hydroxyethyl)-2-(triethylsilyl)-1H-indole-5-carbonitrile (0.873 g; 2.91 mmol) in THF (6 mL) was added to a solution of triphenylphosphine (1.52 g; 5.81 mmol) and perbromomethane (1.93 g; 5.81 mmol) in THF (30 mL) pre-stirred for 30 minutes. The resulting mixture was stirred at room temperature overnight, filtered and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 2 to 40% ethyl acetate in heptane) to yield 0.906 g (86%) of the title compound as a white solid.
CC[Si](CC)(CC)c1[nH]c2ccc(C#N)cc2c1CCBr
null
CC[Si](CC)(CC)c1[nH]c2ccc(C#N)cc2c1CCO
BrC(Br)(Br)Br
null
O[CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]#[N:14])[CH:11]=2)[NH:6][C:5]=1[Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:41]C(Br)(Br)Br>C1COCC1>[Br:41][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]#[N:14])[CH:11]=2)[NH:6][C:5]=1[Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17]
0.5
C1CCOC1
null
null
null
85.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
731,742
CC(=O)[O-]
[Na+]
null
null
ord_dataset-eb4226b4f7644a01a737e7547b70014a
2006-01-01T00:09:00
true
0.35 mol (32 mL) of POCl3 was added at 0° C. to a 1.0 mol (77 mL) of DMF (excess of DMF used as solvent). At the end of the addition, the mixture was allowed to warm to room temperature and stirred for 1 h. Then it was cooled again to 0° C. and treated with 3-methyl-2-phenylthiophene (60 g, 0.35 mol). The resulting reaction mixture was allowed to reach room temperature and after 12 h stirring at the same temperature was heated at 80° C. for 2 days. Then it was poured into a mixture of ice and water, added of sodium acetate and extracted with CHCl3 (3×150 mL). The organic phase was separated, washed with water until neutral pH, dried over MgSO4 and evaporated off to dryness. The residue was crystallized. Yield 60.2 g (85%).
Cc1cc(C=O)sc1-c1ccccc1
null
Cc1ccsc1-c1ccccc1
CN(C)C=O
null
O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[CH3:11][C:12]1[CH:16]=[CH:15][S:14][C:13]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])(=O)C.[Na+]>O>[CH:9]([C:15]1[S:14][C:13]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[C:12]([CH3:11])[CH:16]=1)=[O:10]
1
O=P(Cl)(Cl)Cl
O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
608,534
O=C([O-])[O-]
[K+]
null
null
ord_dataset-73916d628db147c89020b3baac642d48
2003-01-01T00:09:00
true
4-hydroxy-8-methoxynaphthalene-1-carbaldehyde (1 g, 5 mmol) was dissolved in DMF (15 mL). To this mixture potassium carbonate (3.4 g, 25 mmol) and 1,2-dibromoethane (4 mL, 50 mmol) were added and the resulting mixture was stirred at room temperature for 16 hours. Water. (150 mL) was added and the resulting mixture was extracted with ethyl acetate (3×90 mL). The combined organic extracts were washed with saturated sodium chloride (100 mL), dried (MgSO4) and evaporated in vacuo to afford 1.13 g (74%) of 4-(2-bromoethoxy)-8-methoxynaphthalene-1-carbaldehyde.
COc1cccc2c(OCCBr)ccc(C=O)c12
null
BrCCBr
COc1cccc2c(O)ccc(C=O)c12
null
[OH:1][C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[C:5]([CH:14]=[O:15])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Br:22][CH2:23][CH2:24]Br.O>CN(C=O)C>[Br:22][CH2:23][CH2:24][O:1][C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[C:5]([CH:14]=[O:15])=[CH:4][CH:3]=1
16
CN(C)C=O
O
null
25
73.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
763,891
null
null
null
null
ord_dataset-7a8649d55889427e85b208ae89475895
2007-01-01T00:04:00
true
Example 51 was prepared from 2,2-diphenylpropanoic acid and N-{5-[1-(3-aminopropyl)-4-piperidinyl]-2-fluorophenyl}-2-methylpropanamide according to the procedures described in Scheme 9: 1H NMR (400 MHz, CDCl3) δ 8.27–8.13 (m, 1H), 8.04 (s, 1H), 7.62 (s, 1H), 7.50–7.39 (m, 1H), 7.39–7.16 (m, 7H), 7.12–6.90 (m, 2H), 6.79–6.60 (br, 1H), 4.94–4.61 (br, 1H), 3.60–3.22 (m, 4H), 2.89–2.76 (m, 2H), 2.76–2.55 (m, 4H), 2.55–2.34 (m, 3H), 2.14–1.82 (m, 3H), 2.00 (s, 3H), 1.26 (d, 6H, J=6.4 Hz); ESMS m/e: 530.4 (M+H)+; Anal. Calc. for (HCl salt) C33H41ClFN3O2.0.24CHCl3.0.96H2O: C, 65.23; H, 7.11; N, 6.86. Found: C, 64.96; H, 7.36; N, 6.87.
CC(C)C(=O)Nc1cc(C2CCN(CCCNC(=O)C(C)(c3ccccc3)c3ccccc3)CC2)ccc1F
null
CC(C(=O)O)(c1ccccc1)c1ccccc1
CC(C)C(=O)Nc1cc(C2CCN(CCCN)CC2)ccc1F
null
[C:1]1([C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([CH3:11])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH:25]([C:28]2[CH:29]=[CH:30][C:31]([F:40])=[C:32]([NH:34][C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH:33]=2)[CH2:24][CH2:23]1>>[F:40][C:31]1[CH:30]=[CH:29][C:28]([CH:25]2[CH2:24][CH2:23][N:22]([CH2:21][CH2:20][CH2:19][NH:18][C:8](=[O:10])[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH3:11])[CH2:27][CH2:26]2)=[CH:33][C:32]=1[NH:34][C:35](=[O:39])[CH:36]([CH3:37])[CH3:38]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,259,091
O=S(=O)(O)O
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
(±)-{8-Fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydroquinazolin-4-yl}acetic acid (54 g) is dissolved in methanol (540 g), then concentrated sulphuric acid (7.85 ml) is added. The mixture is stirred under reflux for 26 h, then cooled and concentrated in vacuo to ca. one third of the original volume. Water (150 ml) and dichloromethane (150 ml) are added, then the phases are separated. The organic phase is extracted with saturated sodium hydrogencarbonate solution (two times 140 ml), dried over sodium sulphate and concentrated to give a foamy residue. This is dissolved twice in succession in ethanol (150 ml each) and concentrated, and subsequently dried for 18 h in vacuo using entraining nitrogen. A total of 41.6 g of methyl {8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate are thus obtained as an amorphous solid, corresponding to 75.2% of theory.
COC(=O)CC1c2cccc(F)c2N=C(N2CCN(c3cccc(OC)c3)CC2)N1c1cc(C(F)(F)F)ccc1OC
null
COc1cccc(N2CCN(C3=Nc4c(F)cccc4C(CC(=O)O)N3c3cc(C(F)(F)F)ccc3OC)CC2)c1
CO
null
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:12]1[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH2:14][CH2:13]1)[N:8]([C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1[O:36][CH3:37])[CH:7]2[CH2:38][C:39]([OH:41])=[O:40].S(=O)(=O)(O)O.[CH3:47]O>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:12]1[CH2:13][CH2:14][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH2:16][CH2:17]1)[N:8]([C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1[O:36][CH3:37])[CH:7]2[CH2:38][C:39]([O:41][CH3:47])=[O:40]
null
CCO
null
null
null
75.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
5,281
CCOC(=O)N1C2CCC1CN(C)C2
Cl
null
null
ord_dataset-a5669edbeffe43bf8514c1bfede8f882
1976-01-01T00:04:00
true
3-Methyl-3,8-diazabicyclo[3.2.1]octane dihydrochloride (3.0 g, 0.0151 mole), prepared as described in Example 5, was reacted with 1.21 ml (0.0151 mole) ethyl isocyanate in a procedure as described for 8-carbethoxy-3-methyl-3,8-diazabicyclo[3.2.1]octane in Example 6. The crude desired product, as the free base, was purified by chromatography on alumina with chloroform elution. An hydrochloride salt was made by treatment of a solution of the free base in diethyl ether with ethanolic hydrogen chloride and filtering to collect 1.0 g (28% yield) white solid exhibiting a dual melting point of 100°-140° C and 191°-202° C until dried 2 hours at 126° C in vacuo after which the desired product hydrochloride salt melted at 205°-215° C.
CCNC(=O)N1C2CCC1CN(C)C2
null
CCN=C=O
CN1CC2CCC(C1)N2
null
Cl.Cl.[CH3:3][N:4]1[CH2:10][CH:9]2[NH:11][CH:6]([CH2:7][CH2:8]2)[CH2:5]1.[CH2:12]([N:14]=[C:15]=[O:16])[CH3:13].C(N1C2CCC1CN(C)C2)(OCC)=O>>[CH2:12]([NH:14][C:15]([N:11]1[CH:9]2[CH2:8][CH2:7][CH:6]1[CH2:5][N:4]([CH3:3])[CH2:10]2)=[O:16])[CH3:13]
null
null
null
null
null
null
33.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
764,540
O=C([O-])[O-]
[K+]
null
null
ord_dataset-7a8649d55889427e85b208ae89475895
2007-01-01T00:04:00
true
Potassium carbonate (122 mg, 0.883 mmol) and then n-propyl bromide (40 μl, 0.440 mmol) were added to a solution of the N-(8-azabicyclo[3.2.1]oct-3-yl)-4-methyl-1H-indazol-5-amine (74 mg, 0.289 mmol) obtained in Example 501 in N,N-dimethylformamide (2 ml), and the resulting mixture was stirred at room temperature for 15 hours. After the solid was removed by filtration, the solvent was distilled off under reduced pressure as an azeotrope with toluene. The residue was purified by a silica gel column chromatography (chloroform/methanol/triethylamine=100/1/5) and then a preparative thin-layer chromatography (200×200×0.5 mm, 2 plates, eluent: chloroform/methanol/triethylamine=100/5/5) to obtain N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-4-methyl-1H-indazol-5-amine (36 mg, 42%).
CCCN1C2CCC1CC(Nc1ccc3[nH]ncc3c1C)C2
null
CCCBr
Cc1c(NC2CC3CCC(C2)N3)ccc2[nH]ncc12
null
C(=O)([O-])[O-].[K+].[K+].[CH3:7][CH2:8][CH2:9]Br.[CH:11]12[NH:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][CH:13]([NH:19][C:20]1[C:21]([CH3:29])=[C:22]3[C:26](=[CH:27][CH:28]=1)[NH:25][N:24]=[CH:23]3)[CH2:12]2>CN(C)C=O>[CH2:9]([N:18]1[CH:15]2[CH2:16][CH2:17][CH:11]1[CH2:12][CH:13]([NH:19][C:20]1[C:21]([CH3:29])=[C:22]3[C:26](=[CH:27][CH:28]=1)[NH:25][N:24]=[CH:23]3)[CH2:14]2)[CH2:8][CH3:7]
15
CN(C)C=O
null
null
25
41.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,749,596
null
null
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
A slurry of 8-bromo-2-chloro-3-(pyridin-3-yl)quinazolin-4(3H)-one (403b, 0.20 g, 0.594 mmol) and isopropylamine (2.04 mL, 23.77 mmol) was sealed and heated in an 80° C. oil bath for 1 h. The reaction was partitioned between sat'd aq. NaHCO3 and DCM. The aqueous layer was extracted with DCM 2 times, and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 8-bromo-2-(isopropylamino)-3-(pyridin-3-yl)quinazolin-4(3H)-one (0.22 g, 0.612 mmol, 103% yield) as a light yellow foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.83 (1H, d, J=3.5 Hz), 8.60 (1H, br. s.), 8.08 (1H, dd, J=7.8, 1.6 Hz), 7.94 (1H, dd, J=7.7, 1.5 Hz), 7.66-7.75 (1H, m), 7.60 (1H, dd, J=8.0, 4.9 Hz), 7.04 (1H, t, J=7.8 Hz), 4.32-4.49 (1H, m), 3.80 (1H, d, J=6.3 Hz), 1.23 (6H, m). m/z (ESI, +ve) 359.0/361.0 (M+H)+.
CC(C)Nc1nc2c(Br)cccc2c(=O)n1-c1cccnc1
null
O=c1c2cccc(Br)c2nc(Cl)n1-c1cccnc1
CC(C)N
null
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[C:7]2=[O:19].[CH:20]([NH2:23])([CH3:22])[CH3:21]>>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:23][CH:20]([CH3:22])[CH3:21])[N:8]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[C:7]2=[O:19]
null
null
null
null
80
null
103
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,481,372
Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
[Cu]I
null
null
ord_dataset-c3c1091f873b4f40827973a6f1f9b685
2014-01-01T00:09:00
true
Into a round bottom flask was added 3-ethynyl-2-fluoropyridine (0.3 g, 0.002 mol), 4-fluoro-1-iodo-2-nitrobenzene (0.675 g, 0.00253 mol), bis(triphenylphosphine)palladium(II) chloride (0.09 g, 0.1 mmol), copper(I) iodide (0.04 g, 0.2 mmol), and triethylamine (0.52 mL, 3.7 mmol) in N,N-dimethylformamide (4 mL). The reaction was stirred at room temperature for 2 hours. The reaction was extracted with ethyl acetate, and the combined organic extracts were washed with brine (3×), dried over MgSO4, and purified by column chromatography on silica gel (10% ethyl acetate 90% hexanes), to give 0.443 g of product. 1H NMR (400 MHz, CDCl3): δ 8.44-8.50 (m, 1H), 7.99-8.02 (m, 1H), 7.79-7.90 (m, 1H), 7.78-7.82 (m, 1H), 7.37-7.42 (m, 1H), 7.23-7.29 (m, 1H). MS [M+H]=261.0.
O=[N+]([O-])c1cc(F)ccc1C#Cc1cccnc1F
null
C#Cc1cccnc1F
O=[N+]([O-])c1cc(F)ccc1I
null
[C:1]([C:3]1[C:4]([F:9])=[N:5][CH:6]=[CH:7][CH:8]=1)#[CH:2].[F:10][C:11]1[CH:16]=[CH:15][C:14](I)=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=1.C(N(CC)CC)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:9][C:4]1[C:3]([C:1]#[C:2][C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][C:13]=2[N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=[CH:6][N:5]=1
2
CN(C)C=O
CCN(CC)CC
null
25
null
85.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
64,415
[Na+]
null
null
null
ord_dataset-d986d6c6630b41ee8d401fd85be47701
1980-01-01T00:04:00
true
To a warm mixture of 7 g. (18.3 m moles) sodium 4-(hexadecylamino)benzoate in 100 ml. ethanol is added 4.7 g. (18.3 m moles) ethyl α-tosyloxypropionate. After 17 hours at reflux, the cooled solution is diluted with an equal volume of water and the resultant precipitate is filtered. After washing with cold ethanol and drying, the product is crystallized from acetonitrile to yield the product as colorless crystals.
CCCCCCCCCCCCCCCCNc1ccc(C(=O)OC(C)C(=O)OCC)cc1
null
CCCCCCCCCCCCCCCCNc1ccc(C(=O)[O-])cc1
CCOC(=O)C(C)OS(=O)(=O)c1ccc(C)cc1
null
[CH2:1]([NH:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([O-:24])=[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].[Na+].C(O)C.S(O[CH:42]([CH3:48])[C:43]([O:45][CH2:46][CH3:47])=[O:44])(C1C=CC(C)=CC=1)(=O)=O>O>[CH2:1]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH:42]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:48])=[O:23])=[CH:25][CH:26]=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]
null
O
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
644,272
COC(=N)c1ccc(O)cc1
Cl
null
null
ord_dataset-c975a50a7600448fabd558f4a94a3e29
2004-01-01T00:08:00
true
Ethyl 3-amino-4-cyclohexylaminobenzoate (130 g) obtained in Example 1, Step 3, and methyl 4-hydroxybenzimidate hydrochloride (139 g) were added to methyl alcohol (1500 ml), and the mixture was refluxed under heating for 4 hr. The reaction mixture was allowed to cool and the precipitated crystals were collected by filtration to give the title compound (131 g, yield 72%).
CCOC(=O)c1ccc2c(c1)nc(-c1ccc(O)cc1)n2C1CCCCC1
null
CCOC(=O)c1ccc2c(c1)nc(-c1ccc(Oc3cccc(Br)c3)cc1)n2C1CCCCC1
null
null
BrC1C=C(C=CC=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:15]3[CH:23]=[CH:24][C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:26][C:14]=3[N:13]=2)=[CH:8][CH:7]=1.Cl.OC1C=CC(C(=N)OC)=CC=1>CO>[CH:17]1([N:16]2[C:15]3[CH:23]=[CH:24][C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:26][C:14]=3[N:13]=[C:12]2[C:9]2[CH:10]=[CH:11][C:6]([OH:5])=[CH:7][CH:8]=2)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1
null
CO
null
null
null
143.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
898,550
CC[SiH](CC)CC
O=C([O-])[O-]
[Na+]
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
rac-6-Chloro-3-hydroxy-3-pyridin-3-yl-1,3-dihydro-indol-2-one (0.27 g, 1.0 mmol) (from Example 39a supra) was suspended in a mixture of triethylsilane (0.49 mL, 3.0 mmol) (Aldrich) and trifluoroacetic acid (1.77 g, 15.0 mmol) (Aldrich) and heated in an 78° C. oil bath for overweekend. After cooling to room temperature, the mixture was diluted with ethyl acetate and treated with solid sodium carbonate (1.0 g). After stirring for 30 minutes, mixture was extracted with water and brine. Aqueous layers were back washed with ethyl acetate. Organic layers were combined, dried (Na2SO4), filtered and concentrated to obtain rac-6-chloro-3-pyridin-3-yl-1,3-dihydro-indol-2-one (Yield 0.1 g, 40%) as yellow oil and carried out for the next step without further purification.
O=C1Nc2cc(Cl)ccc2C1c1cccnc1
null
O=C1Nc2cc(Cl)ccc2C1(O)c1cccnc1
null
null
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](O)([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
0.5
CCOC(C)=O
O=C(O)C(F)(F)F
null
78
null
40.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,189,048
O=C([O-])[O-]
[Na+]
null
null
ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff
2012-01-01T00:07:00
true
3.48 g (11.2 mmol) of 3-methyl-1-oxy-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester [prepared from 3-methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester (intermediate 1A) by reaction with 3-chloro-perbenzoic acid in analogy to the procedure described for the preparation of intermediate 1C] was added at RT while stirring to 20.4 ml=34.25 g (223.3 mmol) of phosphorus oxychloride and the reaction mixture was warmed up to 50° C. After 2 hours, it was cooled down to RT and poured into crashed ice. This solution was carefully neutralized with solid sodium carbonate and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (heptane/CH2Cl2 1:1 to 0:1) to give 2.52 g (68%) 6-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester as light yellow oil; [MS: 330.0 (MH+, 1Cl)] and 1.10 g (30%) 4-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester as colorless solid. MS: 330.0 (MH+, 1Cl).
COC(=O)c1nc(Cl)c(-c2cccc(C(F)(F)F)c2)cc1C
null
O=C(OO)c1cccc(Cl)c1
COC(=O)c1ncc(-c2cccc(C(F)(F)F)c2)cc1C
null
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[CH:7][N:6]=1)=[O:4].[Cl:22]C1C=CC=C(C(OO)=O)C=1.P(Cl)(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[C:7]([Cl:22])[N:6]=1)=[O:4]
2
O=P(Cl)(Cl)Cl
null
null
50
null
68
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
493,057
null
null
null
null
ord_dataset-3f9174c7efcb4f31becbd3516cde9572
2001-01-01T00:02:00
true
(Step 2) In 85 ml of dry tetrahydrofuran was dissolved 17 g of 2,4-dichloro-6-phenyl-1,3,5-triazine. To this solution on an ice-water bath was added 135 ml of 1M methylmagnesium bromide-tetrahydrofuran dropwise over about 30 minutes. After completion of dropwise addition, the mixture was stirred at room temperature for 2 hours. This reaction mixture was poured into iced water and extracted with ethyl acetate. The extract was washed with water, dried over MgSO4, and concentrated. The residue was purified with silica gel column chromatography to provide 3.6 g of the title compound as white crystals.
Cc1nc(Cl)nc(-c2ccccc2)n1
null
Clc1nc(Cl)nc(-c2ccccc2)n1
C[Mg]Br
null
[Cl:1][C:2]1[N:7]=[C:6](Cl)[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]=1.[CH3:15][Mg]Br.O1CCCC1.O>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH3:15])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]=1
2
C1CCOC1
O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,584,052
CN(C)C(On1nnc2ccccc21)=[N+](C)C
Cl
F[B-](F)(F)F
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
The mixture of step D product, 2-20-e, (2.5 g, 7.7 mmol), ethyl 2-aminoacetate hydrochloride (1.29 g, 9.3 mmol), TBTU (2.98 g, 9.3 mmol), DIPEA (2.0 g, 15.5 mmol) in DMSO (20 mL) and stirred at the ambient temperature overnight. Then the reaction mixture was added ice-water (40 mL), extracted with DCM (30 mL×2). The organic phase was concentrated to give a residue, which was purified by column chromatography with DCM:MeOH=150:1 to obtain 2-20 (330 mg, 11%). 1H NMR (300 MHz, DMSO-d6): δ 1.18-1.22 (t, J=6 Hz, 3H), 4.0-4.02 (d, J=6 Hz, 2H), 4.11-4.14 (q, J=6.0 Hz, 2H), 5.0-5.02 (d, J=6.0 Hz, 1H), 7.48-7.57 (m, 4H), 7.87 (m, 3H), 8.55 (br s, 1H), 9.48 (m, 1H), 9.87 (br s, 1H), 13.54 (br s, 1H). LC-MS: (M+H)+ 409.
CCOC(=O)CNC(=O)c1ncc(C(=O)NCc2cccc3ccccc23)c(O)n1
null
CCOC(=O)CN
O=C(O)c1ncc(C(=O)NCc2cccc3ccccc23)c(O)n1
null
[OH:1][C:2]1[C:7]([C:8](=[O:21])[NH:9][CH2:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)=[CH:6][N:5]=[C:4]([C:22]([OH:24])=O)[N:3]=1.Cl.[NH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CS(C)=O>[CH2:31]([O:30][C:28](=[O:29])[CH2:27][NH:26][C:22]([C:4]1[N:3]=[C:2]([OH:1])[C:7]([C:8](=[O:21])[NH:9][CH2:10][C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:18]=[CH:19][CH:20]=2)=[CH:6][N:5]=1)=[O:24])[CH3:32]
null
CCN(C(C)C)C(C)C
CS(C)=O
null
0
null
10.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
509,389
[Pd]
null
null
null
ord_dataset-85c00026681b46f89ef8634d2b8618c3
2001-01-01T00:07:00
true
To a suspension of 10% palladium on carbon (1.5 g) in ethyl acetate (200 mL) at room temperature under argon was added a solutioin of 2-(1,4-Dioxaspiro[4.5]dec-7-en-8-yl)benzonitrile (8.9 g, 36.7 mmol) in ethyl acetate (50 mL). Hydrogen gas was then bubbled into the reaction mixture until all the starting material was consumed. The reaction was filtered through celite to remove the catalyst and the solution concentrated to give the product as a colorless oil.
N#Cc1ccccc1C1CCC2(CC1)OCCO2
null
N#Cc1ccccc1C1=CCC2(CC1)OCCO2
null
null
[O:1]1[C:5]2([CH2:10][CH2:9][C:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[CH:7][CH2:6]2)[O:4][CH2:3][CH2:2]1>[Pd].C(OCC)(=O)C>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1
null
CCOC(C)=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
348,242
[Co]
null
null
null
ord_dataset-66f304805e5d47fc8d3c722b1bd8dfa2
1996-01-01T00:12:00
true
30 g of 91.7% pure 2-chloro-5-cyanopyridine were hydrogenated in 100 ml of methylformate using 7 g of Raney cobalt analogously to Example 2. 2-Chloro-5-(formylaminomethyl)pyridine was obtained in a yield of 92.6% of theory, in addition to 2.9% of theory of 2-chloro-5-(aminomethyl)pyridine.
NCc1ccc(Cl)nc1
O=CNCc1ccc(Cl)nc1
N#Cc1ccc(Cl)nc1
COC=O
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.[CH3:10][O:11]C=O>[Co]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][CH:10]=[O:11])=[CH:4][N:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH2:9])=[CH:4][N:3]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,280,084
null
null
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
As described for example 29e, 5-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-pyridine-2-carboxylic acid ethyl ester (75 mg, 0.2 mmol) was converted, using 4-aminotetrahydropyran instead of isopropylamine, to the title compound (9 mg, 10%), which was obtained as a colourless gum. MS: m/e=428.3 [M+H]+.
O=C(NC1CCOCC1)c1ccc(OCc2c(-c3ccc(F)cc3)noc2CO)cn1
null
CCOC(=O)c1ccc(OCc2c(-c3ccc(F)cc3)noc2CO)cn1
NC1CCOCC1
null
C(O[C:4]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[C:15]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:16][O:17][C:18]=2[CH2:19][OH:20])=[CH:8][N:7]=1)=[O:5])C.[NH2:28][CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>>[O:32]1[CH2:33][CH2:34][CH:29]([NH:28][C:4]([C:6]2[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]3[C:15]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)=[N:16][O:17][C:18]=3[CH2:19][OH:20])=[CH:8][N:7]=2)=[O:5])[CH2:30][CH2:31]1
null
null
null
null
null
null
10
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,059,202
CCCC[N+](CCCC)(CCCC)CCCC
null
null
null
ord_dataset-373415d3e0e54004837cf4831e67666f
2011-01-01T00:05:00
true
Tetrabutyl-ammonium 2-[(3aR,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-ethanesulfonate (250.0 mg, 0.0003481 mol) was dissolved in methylene chloride (5.00 mL, 0.0780 mol) and N,N-dimethylformamide (100.0 μL, 0.001292 mol). Thionyl chloride (228 μL, 0.00313 mol) was added and the reaction was stirred at 0° C. for 45 minutes, concentrated in vacuo to dryness and followed by azeotroping with toluene. The residue was purified by flash chromatography (10% THF in DCM) to yield product (115 mg, 78%).
CC1(C)O[C@@H]2[C@H](O1)[C@@H](CCS(=O)(=O)Cl)O[C@H]2n1cnc2c(Cl)ncnc21
null
ClCCl
CC1(C)O[C@@H]2[C@H](O1)[C@@H](CCS(=O)(=O)[O-])O[C@H]2n1cnc2c(Cl)ncnc21
null
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][CH2:22][S:23]([O-:26])(=O)=[O:24])[O:12]1.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)[Cl:45].CN(C)C=O.S(Cl)(Cl)=O>>[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][CH2:22][S:23]([Cl:45])(=[O:26])=[O:24])[O:12]1
0.75
CN(C)C=O
O=S(Cl)Cl
null
0
78.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
988,202
CC(C)N=C=NC(C)C
null
null
null
ord_dataset-35b56288528641309a040cc2b6710b61
2010-01-01T00:08:00
true
0.16 mmol of 2-phenoxymethyl-1-(4-trifluoromethoxy-benzyl)-1H-benzoimidazole-5-carboxylic acid were dissolved in 1 ml THF with 1 eq. DIC. After 15 min 1.5 eq of butylamine was added and the reaction stirred at room temperature for 16 h. The crude material was purified via reversed phase preparative HPLC. MS(ISP) 498.3 (M+H)+.
CCCCNC(=O)c1ccc2c(c1)nc(COc1ccccc1)n2Cc1ccc(OC(F)(F)F)cc1
null
CCCCN
O=C(O)c1ccc2c(c1)nc(COc1ccccc1)n2Cc1ccc(OC(F)(F)F)cc1
null
[O:1]([CH2:8][C:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[C:12]2[CH:26]=[CH:27][C:28]([C:30]([OH:32])=O)=[CH:29][C:11]=2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)N=C=NC(C)C.[CH2:42]([NH2:46])[CH2:43][CH2:44][CH3:45]>C1COCC1>[CH2:42]([NH:46][C:30]([C:28]1[CH:27]=[CH:26][C:12]2[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([F:23])([F:25])[F:24])=[CH:17][CH:16]=3)[C:9]([CH2:8][O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[N:10][C:11]=2[CH:29]=1)=[O:32])[CH2:43][CH2:44][CH3:45]
16
C1CCOC1
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,258,943
CC(=O)O[BH-](OC(C)=O)OC(C)=O
[Na+]
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
65 mg (53%) of target compound was obtained by using a method same as in Example 1 by using 3-(5-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl)propanal (75 mg, 0.245 mmol), 1-(2-fluorophenyl)piperazine (44 mg, 0.245 mmol), DIPEA (0.064 mL, 0.368 mmol) and NaBH(OAc)3 (156 mg, 0.735 mmol).
COc1ccc(-c2cc(CCCN3CCN(c4ccccc4F)CC3)nn2-c2ccccc2)cc1
null
Fc1ccccc1N1CCNCC1
COc1ccc(-c2cc(CCC=O)nn2-c2ccccc2)cc1
null
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=[C:11]([CH2:20][CH2:21][CH:22]=O)[CH:10]=2)=[CH:5][CH:4]=1.[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][N:34]([CH2:22][CH2:21][CH2:20][C:11]2[CH:10]=[C:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:12]=2)[CH2:33][CH2:32]1
null
CCN(C(C)C)C(C)C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,115,050
C[Si](C)(C)I
null
null
null
ord_dataset-4226e9b4f9f845db967ed997270dcafc
2011-01-01T00:12:00
true
A mixture of 1 mmol of 7-methoxy-2,3,6′,7′-tetrahydro-5′H-spiro[chromene-4,8′-imidazo[1,5-a]pyridine] and 5 ml of trimethylsilyl iodide in 20 ml of acetonitrile is heated at reflux for 24 hours. 5 ml of methanol are added cautiously and the mixture is heated at reflux for a further 30 minutes. The reaction mixture is evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60F) on the basis of the Rf value.
Oc1ccc2c(c1)OCCC21CCCn2cncc21
null
COc1ccc2c(c1)OCCC21CCCn2cncc21
null
null
C[O:2][C:3]1[CH:8]=[C:7]2[O:9][CH2:10][CH2:11][C:12]3([CH2:17][CH2:16][CH2:15][N:14]4[CH:18]=[N:19][CH:20]=[C:13]34)[C:6]2=[CH:5][CH:4]=1.C[Si](I)(C)C.CO>C(#N)C>[CH:20]1[N:19]=[CH:18][N:14]2[CH2:15][CH2:16][CH2:17][C:12]3([C:6]4[C:7](=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=4)[O:9][CH2:10][CH2:11]3)[C:13]=12
null
CC#N
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,225,998
null
null
null
null
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
2012-01-01T00:11:00
true
Ethyl N-(6-chloro-2-methoxyquinoxalin-3-yl)carbamate and 1-(4-fluorophenyl)piperazine were reacted by the same way with the example 22 to obtain the titled compound (yield, 77%). 1H NMR (300 MHz, CDCl3): δ 3.13-3.20 (m, 4H), 3.77 (s, 3H), 4.14 (s, 4H), 6.88-7.02 (m, 4H), 7.20-7.24 (m, 1H), 7.36-7.44 (m, 1H), 7.50-7.67 (m, 1H), 7.80 (s, 1H).
COc1nc2ccc(Cl)cc2nc1NC(=O)N1CCN(c2ccc(F)cc2)CC1
null
CCOC(=O)Nc1nc2cc(Cl)ccc2nc1OC
Fc1ccc(N2CCNCC2)cc1
null
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:30]1[CH2:29][CH2:28][N:27]([C:24]3[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=3)[CH2:32][CH2:31]1)=[O:19])=[N:5]2
null
null
null
null
null
77
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,765,739
Cl
O=C([O-])[O-]
[K+]
null
ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8
2016-01-01T00:09:00
true
The title compound was prepared according to the procedure described in Intermediate-19 by using 3-fluoro-5-(trifluoromethyl)benzonitrile (2.00 g, 10.0 mmol), hydroxyl amine HCl (1.09 g, 15 mmol) and potassium carbonate (2.2 g, 15 mmol), ethanol (20 mL) to afford 0.900 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 6.10 (s, 2H), 7.69 (d, J=7.8 Hz, 1H), 7.79 (d, J=10.2 Hz, 1H), 10.03 (s, 1H); MS (m/z): 223.17 (M+H)+.
NC(=NO)c1cc(F)cc(C(F)(F)F)c1
null
N#Cc1cc(F)cc(C(F)(F)F)c1
NO
null
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)[C:5]#[N:6].Cl.[OH:15][NH2:16].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=1)[C:5](=[N:16][OH:15])[NH2:6]
null
CCO
null
null
null
40.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,281,243
Cl
[K+]
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
To a suspension of ethyl 5-methoxy-4-methyl-1H-indole-2-carboxylate (712 mg, 3.05 mmol) in toluene (10 mL) was added a 1 M solution of KOtBu in THF (3.97 mL, 3.97 mmol). The reaction mixture was stirred at room temperature for 5 min, methyl acrylate (825 μL, 9.15 mmol) was added. The reaction was stirred at reflux overnight and neutralized with 1 N HCl aqueous solution. The solid was collected and divided into three microwave vial. Each was added AcOH (8 mL) and H2O (1 mL), and heated at 180° C. for 15 min under microwave irradiation. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title compound as a yellow solid (500 mg). LCMS m/z=216.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 2.45 (s, 3H), 3.21 (t, J=6.5 Hz, 2H), 3.68 (s, 3H), 4.40 (t, J=6.2 Hz, 2H), 6.98 (s, 1H), 7.13 (d, J=9.0 Hz, 1H), 7.23 (d, J=9.0 Hz, 1H).
COc1ccc2c(cc3n2CCC3=O)c1C
null
CCOC(=O)c1cc2c(C)c(OC)ccc2[nH]1
CC(C)(C)[O-]
null
[CH3:1][O:2][C:3]1[C:4]([CH3:17])=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([O:14]CC)=O)=[CH:6]2.[CH3:18][C:19]([O-])(C)C.[K+].C1COCC1.C(OC)(=O)C=C.Cl>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]2[N:8]3[CH2:18][CH2:19][C:12](=[O:14])[C:7]3=[CH:6][C:5]=2[C:4]=1[CH3:17]
0.08
C1CCOC1
Cc1ccccc1
C=CC(=O)OC
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,116,339
[Ni]
null
null
null
ord_dataset-4226e9b4f9f845db967ed997270dcafc
2011-01-01T00:12:00
true
7-(Azidomethyl)quinoline (1.1 g, 5.7 mmol) was hydrogenated (1 atm) in the presence of Raney nickel (1.5 g, 26 mmol) in methanol (30 mL) until completion of the reaction. Catalyst was filtered off and the filtrate was concentrated under reduced pressure to a yellow oil which was dissolved in EtOAc (32 mL) and extracted with 1N hydrochloric acid (3×32 mL). The combined acidic aqueous phases were adjust to pH˜10 with 1N sodium hydroxide solution, and extracted with EtOAc (3×35 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford a white solid (0.89 g, 94%).
NCc1ccc2cccnc2c1
null
[N-]=[N+]=NCc1ccc2cccnc2c1
null
null
[N:1]([CH2:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[CH:10][CH:11]=[N:12]2)=[CH:7][CH:6]=1)=[N+]=[N-]>[Ni].CO>[N:12]1[C:13]2[C:8](=[CH:7][CH:6]=[C:5]([CH2:4][NH2:1])[CH:14]=2)[CH:9]=[CH:10][CH:11]=1
null
CO
null
null
null
null
98.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
54,123
[H-]
[Na+]
null
null
ord_dataset-053897d9b1744303b2fdfe3e796ca27b
1979-01-01T00:04:00
true
A solution of 4 g (14.7 mmoles) of 4a-(m-methoxyphenyl)-1,3-diketo-trans-decahydroisoquinoline in 50 ml of anhydrous dimethylformamide was added dropwise to 700 mg of a 55% suspension of sodium hydride in mineral oil in 50 ml of dimethylformamide at 70°. The reaction mixture was heated for 1 hour after the addition was complete and then cooled to 25°. 3,3-Dimethylallyl bromide (2.37 g, 15.8 mmoles) in 10 ml of dimethylformamide was added dropwise and the solution stirred overnight at 25°. After heating at 80° for 1 hour it was poured into water and extracted with ether to yield 4.74 g of N-(3,3-dimethylallyl)-4a-(m-methoxyphenyl)-1,3-diketo-cis-decahydroisoquinoline (oil), which was evaporatively distilled, bp 225° (0.005 mm).
COc1cccc([C@@]23CCCC[C@@H]2C(=O)N(CC=C(C)C)C(=O)C3)c1
null
COc1cccc([C@@]23CCCC[C@H]2C(=O)NC(=O)C3)c1
CC(C)=CCBr
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@@:9]23[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[C:13](=[O:19])[NH:12][C:11](=[O:20])[CH2:10]3)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH3:23][C:24]([CH3:28])=[CH:25][CH2:26]Br.O>CN(C)C=O>[CH3:23][C:24]([CH3:28])=[CH:25][CH2:26][N:12]1[C:11](=[O:20])[CH2:10][C@@:9]2([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C@H:14]([CH2:15][CH2:16][CH2:17][CH2:18]2)[C:13]1=[O:19]
8
O
CN(C)C=O
null
null
94.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,513,447
Cl[Pd]Cl
[Fe+2]
c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
To (6-chloro-pyridin-3-yl)-{6-fluoro-5-[hydroxy-(4-methoxy-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-carbamic acid tert-butyl ester (72, 105 mg, 0.160 mmol) in 3.8 mL of toluene, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with dichloromethane (13.0 mg, 0.016 mmol) is added under an atmosphere of nitrogen. The reaction is stirred for 5 minutes, then cyclopropylmagnesium bromide (17, 1.60 mL, 1.0 M in tetrahydrofuran, 1.60 mmol) is added slowly. The reaction is heated at 65° C. for 5 hours, then poured into water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (73, 70 mg). MS (ESI) [M+H+]+=563.6.
COc1ncnc2c1c(C(O)c1ccc(Nc3ccc(C4CC4)nc3)nc1F)cn2[Si](C(C)C)(C(C)C)C(C)C
null
COc1ncnc2c1c(C(O)c1ccc(N(C(=O)OC(C)(C)C)c3ccc(Cl)nc3)nc1F)cn2[Si](C(C)C)(C(C)C)C(C)C
Br[Mg]C1CC1
null
C(OC(=O)[N:7]([C:38]1[CH:39]=[N:40][C:41](Cl)=[CH:42][CH:43]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([OH:36])[C:15]2[C:23]3[C:22]([O:24][CH3:25])=[N:21][CH:20]=[N:19][C:18]=3[N:17]([Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])[CH:16]=2)=[C:10]([F:37])[N:9]=1)(C)(C)C.ClCCl.[CH:49]1([Mg]Br)[CH2:51][CH2:50]1.O>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:49]1([C:41]2[N:40]=[CH:39][C:38]([NH:7][C:8]3[N:9]=[C:10]([F:37])[C:11]([CH:14]([C:15]4[C:23]5[C:22]([O:24][CH3:25])=[N:21][CH:20]=[N:19][C:18]=5[N:17]([Si:26]([CH:33]([CH3:35])[CH3:34])([CH:27]([CH3:29])[CH3:28])[CH:30]([CH3:32])[CH3:31])[CH:16]=4)[OH:36])=[CH:12][CH:13]=3)=[CH:43][CH:42]=2)[CH2:51][CH2:50]1
0.08
O
Cc1ccccc1
ClCCl
65
null
77.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,011,092
[Li+]
[OH-]
null
null
ord_dataset-7448b89163bf426c9d9777809ce24cec
2010-01-01T00:11:00
true
A solution of lithium hydroxide monohydrate (2.32 g, 55.1 mmol) in water (100 mL) was added to a solution of methyl 3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoate (7.41 g, 22.0 mmol) in THF (200 mL) and the mixture allowed to stir at RT overnight. The THF was removed in vacuo and the resulting solution partitioned between water (100 mL) and ethyl acetate (250 mL). The ethyl acetate layer was separated, washed with brine and dried (MgSO4). The aqueous layer was then adjusted to pH 7 by addition of 1M hydrochloric acid and extracted with ethyl acetate (75 mL). The ethyl acetate layer was separated, washed with brine and dried (MgSO4). The ethyl acetate layers were combined and evaporated to give the required product (6.404 g).
O=C(O)c1cc(OCc2ccccc2)cc(OC(CF)CF)c1
null
COC(=O)c1cc(OCc2ccccc2)cc(OC(CF)CF)c1
null
null
O.[OH-].[Li+].[F:4][CH2:5][CH:6]([O:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1)[C:13]([O:15]C)=[O:14])[CH2:7][F:8]>O.C1COCC1>[F:4][CH2:5][CH:6]([O:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:19]=1)[C:13]([OH:15])=[O:14])[CH2:7][F:8]
8
O
C1CCOC1
null
25
90.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
2,354
ClP(Cl)(Cl)(Cl)Cl
null
null
null
ord_dataset-a0bc986c3cf848c2a1ea93b297d1ad89
1976-01-01T00:02:00
true
A solution of N-methyl-p-carbmethoxybenzamide in chloroform was treated with phosphorus pentachloride to give E. Then E was reacted with p-carbmethoxybenzoyl hydrazine to yield dimethyl-4,4'-(4-methyl-1,2,4-triazol-3,5-diyl)dibenzoate, (F). Then IV was obtained by reacting F in a similar manner as in Example 1.
COC(=O)c1ccc(-c2nnc(-c3ccc(C(=O)OC)cc3)n2C)cc1
null
COC(=O)c1ccc(C(=O)NN)cc1
CNC(=O)c1ccc(C(=O)OC)cc1
null
[CH3:1][NH:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:5]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[C:21]([C:25]1[CH:34]=[CH:33][C:28]([C:29]([NH:31][NH2:32])=O)=[CH:27][CH:26]=1)([O:23][CH3:24])=[O:22]>C(Cl)(Cl)Cl>[CH3:13][O:12][C:10](=[O:11])[C:7]1[CH:8]=[CH:9][C:4]([C:3]2[N:2]([CH3:1])[C:29]([C:28]3[CH:33]=[CH:34][C:25]([C:21]([O:23][CH3:24])=[O:22])=[CH:26][CH:27]=3)=[N:31][N:32]=2)=[CH:5][CH:6]=1
null
ClC(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,336,578
Cl
N
[Na+]
null
ord_dataset-08852243bba44cb28769a5833f1515fe
2013-01-01T00:09:00
true
20 mL ACN are added to 0.50 g (1.11 mmol) 3-(4-chlorophenyl)-6-chloropyridazine and 3.33 g (22.2 mmol) NaI before 189 μl fuming conc. HCl are added and the mixture is stirred at 80° C. for 4 h. The mixture is alkalised with aq. ammonia solution (32%) diluted with water and extracted with EtOAc. The org. phases are combined, dried with Na2SO4 and the solvent is removed in vacuo. The resulting crude product is triturated with TBME.
Clc1ccc(-c2ccc(I)nn2)cc1
null
Clc1ccc(-c2ccc(Cl)nn2)cc1
[I-]
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][C:11](Cl)=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[Na+].[I-:16].Cl.N>O.C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][C:11]([I:16])=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
4
CC#N
O
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,263,325
C(=NC1CCCCC1)=NC1CCCCC1
CN(C)c1ccccn1
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
A suspension of 1-(tert-butoxycarbonyl)-4-phenylpiperidine-4-carboxylic acid (3.8 g, 10.3 mmol) in a dichloromethane (5 mL) and toluene (30 mL) mixture was treated with 1,3-dicyclohexylcarbodiimide (2.96 g, 14.4 mmol) and stirred for 30 min. The suspension was cooled to 0° C. and treated with (R)-1-(3-bromo-5-(trifluoromethyl)phenyl)ethanol (2.79 g, 10.3 mmol) and dimethylaminopyridine (1.26 g, 10.3 mmol). The ice bath was removed and the suspension stirred at room temperature for 60 h. The reaction mixture was poured into pentane, filtered, and the solids washed several times with pentane. The filtrate was washed with 1 N hydrochloric acid (1×), water (2×), then 1 N sodium hydroxide, then brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel (12% ethyl acetate/hexanes) gave 4.8 g (84%) as a light yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.58 (s, 1H), 7.23-7.33 (m, 6H), 7.19 (s, 1H), 5.80 (q, J=6.6 Hz, 1H), 3.82-3.97 (m, 2H), 2.97-3.09 (m, 2H), 2.44-2.53 (m, 2H), 1.76-2.01 (m, 2H), 1.42 (s, 9H), 1.40 (m, 3H). Mass spec.: 558.06 (MH)+.
C[C@@H](OC(=O)C1(c2ccccc2)CCN(C(=O)OC(C)(C)C)CC1)c1cc(Br)cc(C(F)(F)F)c1
null
CC(C)(C)OC(=O)N1CCC(C(=O)O)(c2ccccc2)CC1
C[C@@H](O)c1cc(Br)cc(C(F)(F)F)c1
null
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[Br:38][C:39]1[CH:40]=[C:41]([C@H:49](O)[CH3:50])[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1.CN(C1C=CC=CN=1)C>C1(C)C=CC=CC=1.ClCCl>[C:17]1([C:11]2([C:14]([O:16][C@@H:49]([C:41]3[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=[C:39]([Br:38])[CH:40]=3)[CH3:50])=[O:15])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
0.5
ClCCl
Cc1ccccc1
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,320,419
Cl
null
null
null
ord_dataset-2d6edb8ffd434003bb508360153bd9bb
2013-01-01T00:07:00
true
The title compound was prepared according to Method B and the experimentals described for compound 92 from 3-(chloromethyl)-2-(4-chlorophenyl)imidazo[1,2-a]pyridine hydrochloride and 2H-benzo[b][1,4]oxazin-3(4H)-one. M/e+ 390 for C22H17ClN3O2 (M+H)+; 1H-NMR (400 MHz, CDCl3) δ 8.32 (d, J=6.9 Hz, 1H), 7.61 (d, J=8.4 Hz, 2H), 7.53 (m, 3H), 7.19 (ddd, J=9.1, 6.9, 1,1 Hz, 1H), 6.82 (m, 3H), 6.48 (m, 1H), 6.26 (d, J=7.7 Hz, 1H), 5.68 (s, 2H), 4.60 (s, 2H) ppm.
O=C1COc2ccccc2N1Cc1c(-c2ccc(Cl)cc2)nc2ccccn12
null
O=C1COc2ccccc2N1
ClCc1c(-c2ccc(Cl)cc2)nc2ccccn12
null
Cl.Cl[CH2:3][C:4]1[N:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]2=[N:6][C:5]=1[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1.[O:20]1[CH2:25][C:24](=[O:26])[NH:23][C:22]2[CH:27]=[CH:28][CH:29]=[CH:30][C:21]1=2>>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:5]2[N:6]=[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]3[C:4]=2[CH2:3][N:23]2[C:24](=[O:26])[CH2:25][O:20][C:21]3[CH:30]=[CH:29][CH:28]=[CH:27][C:22]2=3)=[CH:14][CH:15]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
220,040
Cl
[Na+]
null
null
ord_dataset-6cb04513a4a244c0b612b566096f4b3d
1990-01-01T00:12:00
true
A solution of 0.06 mol of N-(2-allylphenyl)phenylglycine, prepared as described by A. Padwa, H. L. Gingrich, and R. Lim in J. Org. Chem.,1982, 47, 2447-2456, and 0.066 mol of HCl in 100 mL of CH3OH is stirred at reflux for 8 hours. The solution is then cooled and treated with 0.066 mol of sodium bicarbonate. The solvent is removed by rotary evaporator, and the residue is dissolved in diethyl ether, filtered, dried over MgSO4, and filtered. The solvent is removed by rotary evaporator to give N-(2-allylphenyl)phenylglycine methyl ester.
C=CCc1ccccc1N(CC(=O)OC)c1ccccc1
null
C=CCc1ccccc1N(CC(=O)O)c1ccccc1
O=C([O-])O
null
[CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:11][C:12]([OH:14])=[O:13])[CH:2]=[CH2:3].Cl.[C:22](=O)(O)[O-].[Na+]>CO>[CH3:22][O:13][C:12](=[O:14])[CH2:11][N:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:1][CH:2]=[CH2:3]
null
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
49,342
ClCCN1CCOCC1
null
null
null
ord_dataset-0bb2e99daa66408fb8dbd6a0781d241c
1978-01-01T00:12:00
true
By substituting 3-piperazinopropyl chloride for the 1-chloro-2-morpholinoethane in the procedure of Example 5 and utilizing the 2-methyl-4H-pyrazolo[1,5-a]pyrazolo-[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one product of Example 8, 2-methyl-4-(3-piperazino)propyl-4H-pyrazolo[1,5-a]-pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is obtained.
Cc1cc2n(CCCN3CCNCC3)c(=O)c3cnc4[nH]ncc4c3n2n1
null
ClCCCN1CCNCC1
Cc1cc2[nH]c(=O)c3cnc4[nH]ncc4c3n2n1
null
[N:1]1([CH2:7][CH2:8][CH2:9]Cl)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.ClCCN1CCOCC1.[CH3:20][C:21]1[CH:37]=[C:24]2[NH:25][C:26](=[O:36])[C:27]3[CH:32]=[N:31][C:30]4[NH:33][N:34]=[CH:35][C:29]=4[C:28]=3[N:23]2[N:22]=1>>[CH3:20][C:21]1[CH:37]=[C:24]2[N:25]([CH2:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]3)[C:26](=[O:36])[C:27]3[CH:32]=[N:31][C:30]4[NH:33][N:34]=[CH:35][C:29]=4[C:28]=3[N:23]2[N:22]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
951,032
C[O-]
[Na+]
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
Prepared in analogy to that of Example 1(e) from 2,3-dichloro-7-cyano-1-(2-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 437 (M+H)+.
N#Cc1nc(C(=O)NCC(=O)O)c(O)c2c(Cl)c(Cl)n(Cc3ccccc3F)c12
null
CCOC(=O)c1nc(C#N)c2c(c1O)c(Cl)c(Cl)n2Cc1ccccc1F
NCC(=O)O
null
C(O[C:4]([C:6]1[C:7]([OH:27])=[C:8]2[C:16]([Cl:17])=[C:15]([Cl:18])[N:14]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:9]2=[C:10]([C:12]#[N:13])[N:11]=1)=[O:5])C.[NH2:28][CH2:29][C:30]([OH:32])=[O:31].C[O-].[Na+].CO>>[Cl:18][C:15]1[N:14]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])[C:9]2=[C:10]([C:12]#[N:13])[N:11]=[C:6]([C:4]([NH:28][CH2:29][C:30]([OH:32])=[O:31])=[O:5])[C:7]([OH:27])=[C:8]2[C:16]=1[Cl:17]
null
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,284,438
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
To a solution of rac-2-chloro-4-[(4R,5S)-4-(tert-butyldimethylsilyloxy)-3,3,5-trimethyl-2-oxopyrrolidin-1-yl]benzonitrile (121 mg) in THF (5.5 mL) was added tetrabutylammonium fluoride-THF solution (0.5 mL, 1 mol/L), and the mixture was stirred at room temperature for 7 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=10/1→1/2) to give the title compound as a colorless solid (yield: 47.2 mg, 55%).
C[C@H]1[C@H](O)C(C)(C)C(=O)N1c1ccc(C#N)c(Cl)c1
null
C[C@H]1[C@H](O[Si](C)(C)C(C)(C)C)C(C)(C)C(=O)N1c1ccc(C#N)c(Cl)c1
null
null
[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[C@@H:14]([CH3:15])[C@H:13]([O:16][Si](C(C)(C)C)(C)C)[C:12]([CH3:25])([CH3:24])[C:11]2=[O:26])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.O>C1COCC1>[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[C@@H:14]([CH3:15])[C@H:13]([OH:16])[C:12]([CH3:25])([CH3:24])[C:11]2=[O:26])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
7
O
C1CCOC1
null
25
55
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
641,110
C[Si](C)(C)C=[N+]=[N-]
null
null
null
ord_dataset-1c0bae7388cf460091d56129e95b3145
2004-01-01T00:06:00
true
To a stirred solution of 4-hydroxy-3-nitrobenzoic acid (3.00 g, 0.0164 mol) in MeOH-benzene (1:4, v/v) was added dropwise 2.0 M-n-hexane solution of TMSCHN2 (8.2 mL, 0.0164 mol) at room temp. After the resulting solution was stirred for 4 hr at room temp, the mixture was evaporated off in vacuo. The oily residue was chromatographed on silica-gel with CHCl3 as eluent to afford 4.23 g (79%) methyl 4-hydroxy-3-nitrobenzoate as a pale yellow crystalline material.
COC(=O)c1ccc(O)c([N+](=O)[O-])c1
null
O=C(O)c1ccc(O)c([N+](=O)[O-])c1
CCCCCC
null
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[CH3:14]CCCCC.[Si](C=[N+]=[N-])(C)(C)C>CO.C1C=CC=CC=1>[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:14])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
4
CO
c1ccccc1
null
25
79
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
537,075
[Li+]
[OH-]
null
null
ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27
2002-01-01T00:03:00
true
To a suspension of 0.30 g (0.87 mmol) of ethyl 4-[(5,6,7,8-tetrahydro-8,8-dimethyl-5-oxonaphth-2-yl)ethynyl]benzoate (Compound 1) in 4 ml of THF and 2 ml of ethanol was added 2 ml (2 mmol) of LiOH (1N aqueous solution). The reaction mixture was stirred at room temperature for 4 hours, concentrated in vacuo to near dryness, partitioned between EtOAc and 1 ml of water and acidified to pH 4 with 10% HCl. The aqueous layer was extracted with EtOAc and then the organic layer was dried over Na2SO4 and concentrated in vacuo to give the title compound as a light yellow solid.
CC1(C)CCC(=O)c2ccc(C#Cc3ccc(C(=O)O)cc3)cc21
null
CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(C)(C)CCC3=O)cc1
null
null
[CH3:1][C:2]1([CH3:26])[C:11]2[CH:10]=[C:9]([C:12]#[C:13][C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20]CC)=[O:19])=[CH:16][CH:15]=3)[CH:8]=[CH:7][C:6]=2[C:5](=[O:25])[CH2:4][CH2:3]1.[Li+].[OH-]>C1COCC1.C(O)C>[CH3:1][C:2]1([CH3:26])[C:11]2[CH:10]=[C:9]([C:12]#[C:13][C:14]3[CH:15]=[CH:16][C:17]([C:18]([OH:20])=[O:19])=[CH:23][CH:24]=3)[CH:8]=[CH:7][C:6]=2[C:5](=[O:25])[CH2:4][CH2:3]1
4
C1CCOC1
CCO
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
484,777
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-cb5c1a9eddff4790b1bd650617c32d34
2000-01-01T00:11:00
true
Under argon atmosphere, tetrahydrofuran solution of tetrabutylammonium fluoride (1.0M, 2.27 ml, 2.27 mmol) was added dropwise to tetrahydrofuran solution (35 ml) of (3RS,4RS)-4-(4-t-butyldimethylsilyloxyphenyl)-7-methoxymethyloxy-3-[4-(methoxymethyloxy)phenyl]-3-methylthiochroman (856 mg, 1.51 mmol) at 0° C. and the resulting mixture was stirred for 2 hours. After adding water, the reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the solvent. The crude product thus obtained was purified with silica gel column chromatography (ethyl acetate:hexane=1:2) to obtain 682 mg (yield: 100%) of the title compound.
COCOc1ccc(C2(C)CSc3cc(OCOC)ccc3C2c2ccc(O)cc2)cc1
null
COCOc1ccc(C2(C)CSc3cc(OCOC)ccc3C2c2ccc(O[Si](C)(C)C(C)(C)C)cc2)cc1
null
null
O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[C:47]3[C:42](=[CH:43][C:44]([O:48][CH2:49][O:50][CH3:51])=[CH:45][CH:46]=3)[S:41][CH2:40][C:39]2([C:53]2[CH:58]=[CH:57][C:56]([O:59][CH2:60][O:61][CH3:62])=[CH:55][CH:54]=2)[CH3:52])=[CH:34][CH:33]=1)(C(C)(C)C)(C)C>O>[OH:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[C:47]3[C:42](=[CH:43][C:44]([O:48][CH2:49][O:50][CH3:51])=[CH:45][CH:46]=3)[S:41][CH2:40][C:39]2([C:53]2[CH:54]=[CH:55][C:56]([O:59][CH2:60][O:61][CH3:62])=[CH:57][CH:58]=2)[CH3:52])=[CH:34][CH:33]=1
2
C1CCOC1
O
null
null
null
99.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
797,280
CC(C)[N-]C(C)C
[Li+]
null
null
ord_dataset-a2d74266062e4398bc26c4f876903ab8
2007-01-01T00:11:00
true
A solution of lithium diisopropylamide (2M in heptane, 16.9 ml) was added dropwise over 15 min to a stirred solution of 4-benzyl-morpholin-3-one (5.0 g, 26 mmol) and 3-fluorobenzaldehyde (3.55 g, 28.6 mmol) in dried tetrahydrofuran (60 ml) cooled to −70° C. under nitrogen atmosphere. After 1 h at −70° C., the reaction mixture was quenched with aqueous ammonium chloride (100 ml) and extracted with ethyl acetate (100 ml). The extracts were washed with 2M aqueous hydrochloric acid (2×50 ml), brine solution (100 ml) and dried over sodium sulphate. After filtration, the solution was evaporated and the residual oil purified by chromatography on silica eluting with ethyl acetate:hexane 70:30 then ethyl acetate to give diastereomer 1 (2R)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as a solid (3.8 g) followed by diastereomer 2 (2R)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one as an oil (2.13 g). Diastereomer 1 was recrystallised from ethyl acetate (25 ml) n-hexane (100 ml) to give white needles (2.62 g, 32%).
O=C1[C@@H]([C@@H](O)c2cccc(F)c2)OCCN1Cc1ccccc1
O=C1[C@H]([C@H](O)c2cccc(F)c2)OCCN1Cc1ccccc1
O=Cc1cccc(F)c1
O=C1COCCN1Cc1ccccc1
null
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([N:16]1[CH2:21][CH2:20][O:19][CH2:18][C:17]1=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=[O:28]>O1CCCC1>[F:23][C:24]1[CH:25]=[C:26]([C@H:27]([OH:28])[C@H:18]2[O:19][CH2:20][CH2:21][N:16]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:17]2=[O:22])[CH:29]=[CH:30][CH:31]=1.[F:23][C:24]1[CH:25]=[C:26]([C@@H:27]([OH:28])[C@@H:18]2[O:19][CH2:20][CH2:21][N:16]([CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:17]2=[O:22])[CH:29]=[CH:30][CH:31]=1
1
C1CCOC1
null
null
-70
92.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,513,861
null
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
3-Aminopicolinic acid (B-1) (30 g, 217 mmol, 1.0 eq) is suspended in formamide (75 mL, 1.88 mol, 8.66 eq). The resulting mixture is stirred at 140° C. for 1 h and at 170° C. for 1 h and then at 180° C. for an additional 1 h. The mixture is cooled to RT and filtered. The filter cake is washed with water, and dried in vacuo to afford the product, pyrido[3,2-d]pyrimidin-4-ol (B-2).
Oc1ncnc2cccnc12
null
NC=O
Nc1cccnc1C(=O)O
null
[NH2:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:11]([NH2:13])=O>>[N:1]1[C:2]2[CH:7]=[CH:6][CH:5]=[N:4][C:3]=2[C:8]([OH:10])=[N:13][CH:11]=1
1
null
null
null
170
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,496,744
null
null
null
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
A mixture of triethyl orthoformate (4 mL) and (2R,6R,11S)-3-(1H-benzoimidazole-5-carbonyl)-N-hydroxy-6,11-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine-8-carboxamidine (0.25 g) is stirred at 100° C. for 6 h. After cooling to room temperature, the mixture is concentrated and the residue is purified by HPLC on reversed phase (water/MeCN/NH3) to give the title compound as a white solid.
C[C@@H]1[C@H]2Cc3ccc(-c4ncon4)cc3[C@]1(C)CCN2C(=O)c1ccc2[nH]cnc2c1
null
CCOC(OCC)OCC
C[C@@H]1[C@H]2Cc3ccc(C(=N)NO)cc3[C@]1(C)CCN2C(=O)c1ccc2[nH]cnc2c1
null
[CH:1](OCC)(OCC)OCC.[NH:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20]([N:22]3[CH2:29][CH2:28][C@:27]4([CH3:32])[C@H:30]([CH3:31])[C@H:23]3[CH2:24][C:25]3[CH:36]=[CH:35][C:34]([C:37]([NH:39][OH:40])=[NH:38])=[CH:33][C:26]=34)=[O:21])=[CH:19][C:14]=2[N:13]=[CH:12]1>>[NH:11]1[C:15]2[CH:16]=[CH:17][C:18]([C:20]([N:22]3[CH2:29][CH2:28][C@:27]4([CH3:32])[C@H:30]([CH3:31])[C@H:23]3[CH2:24][C:25]3[CH:36]=[CH:35][C:34]([C:37]5[N:38]=[CH:1][O:40][N:39]=5)=[CH:33][C:26]=34)=[O:21])=[CH:19][C:14]=2[N:13]=[CH:12]1
6
null
null
null
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,238,473
O=C([O-])O
[Na+]
null
null
ord_dataset-e96f5a2842f14e5380461c234100f05a
2012-01-01T00:12:00
true
In a glass tube, 250 mg of 1-(benzofuran-3-yl)-2-bromoethanone, 181 mg of 5-bromopyridin-2-ylamine and 105 mg of sodium hydrogencarbonate are dissolved in 15 ml of n-propanol. The tube is closed and heated at 80° C. for 20 h. After cooling, 20 ml of water are added and the reaction mixture is stirred for 1 hour at ambient temperature. A precipitate forms, and is recovered by filtration, washed with water and then with diisopropyl ether, and dried in a desiccator under reduced pressure. 250 mg of compound are obtained.
Brc1ccc2nc(-c3coc4ccccc34)cn2c1
null
O=C(CBr)c1coc2ccccc12
Nc1ccc(Br)cn1
null
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.C(=O)([O-])O.[Na+].O.[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([C:24](=O)[CH2:25]Br)=[CH:16]1>C(O)CC>[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([C:24]2[N:8]=[C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]3[CH:25]=2)=[CH:16]1
1
O
CCCO
null
80
null
76.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
293,466
Cl
Cl[Sn]Cl
null
null
ord_dataset-b90b48a6c23149a1aa2d91b92b1a31e4
1994-01-01T00:07:00
true
A solution of the above nitro mustard (XII; R=H) (2.51 g, 11 mmol) in 12 N HCl (25 mL) was treated portionwise at 25 ° C. with SnCl2.2H2O (9.9 g, 44 mmol), heated on a steam bath at 90° C. for 1 h, then evaporated to dryness under reduced pressure. The residue as shaken vigorously With a mixture of CH2Cl2, 2 N NH4OH and ice, and filtered through a celite pad. Workup of the organic layer gave essentially pure 3-[N-(2-chloroethyl) -N-ethylamino]aniline (XIII; R=H) (1.92 g, 88%) as an oil, which was used immediately.
CCN(CCCl)c1cccc(N)c1
null
CCN(CCCl)c1cccc([N+](=O)[O-])c1
null
null
[Cl:1][CH2:2][CH2:3][N:4]([CH2:14][CH3:15])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-])=O)[CH:6]=1.O.O.Cl[Sn]Cl>Cl>[Cl:1][CH2:2][CH2:3][N:4]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[NH2:11])[CH2:14][CH3:15]
null
O
null
null
90
null
88
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
361,339
O=C([O-])[O-]
[K+]
null
null
ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72
1997-01-01T00:04:00
true
A mixture of methyl-17β-[3-(4-carboxyphenyl)propionyl]-estra-1,3,5(10)-triene-3-carboxylate (0.053 g, 0.11 mmoles), K2CO3 (50 mg, 0.36 mmoles), MeOH (9 ml) and H2O (1 ml) was refluxed under argon. Methanol was evaporated and the residue was acidified with dilute HCl. Extracted with EtOAc. The organic layer was washed with H2O, brine, dried and concentrated. The residue was chromatographed (silica gel) eluting with 1% MeOH in CH2Cl2 containing 1% HOAC to give the title compound as a white solid (40 mg, 80%), mp 285°-290° C.
C[C@]12CC[C@@H]3c4ccc(C(=O)O)cc4CC[C@H]3[C@@H]1CC[C@@H]2C(=O)CCc1ccc(C(=O)O)cc1
null
COC(=O)c1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](C(=O)CCc3ccc(C(=O)O)cc3)CC[C@@H]12
null
null
C[O:2][C:3]([C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C@@H:14]([C:23](=[O:35])[CH2:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([OH:34])=[O:33])=[CH:28][CH:27]=3)[CH2:13][CH2:12]4)[CH2:9][CH2:8][C:7]=2[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].CO>O>[C:32]([C:29]1[CH:28]=[CH:27][C:26]([CH2:25][CH2:24][C:23]([C@H:14]2[CH2:13][CH2:12][C@H:11]3[C@H:10]4[C@H:19]([CH2:18][CH2:17][C@:15]23[CH3:16])[C:20]2[CH:21]=[CH:22][C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]=2[CH2:8][CH2:9]4)=[O:35])=[CH:31][CH:30]=1)([OH:34])=[O:33]
null
O
CO
null
null
79
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,690,398
C[O-]
[Na+]
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
356 mg of sodium methanolate (6.60 mmol, 4.0 eq.) were dissolved in 10 mL of methanol. 403 mg of 5-(dimethylamino)-1-(2-fluorobenzyl)-1H-pyrazole-3-carbonitrile 1-11-1 (1.65 mmol, 1.0 eq.) were dissolved in 20 mL of methanol and added dropwise. The mixture was stirred for one hour at rt. 111.2 mg of ammonium chloride (2.08 mmol, 1.26 eq.) and 377 μL of 100% acetic acid (6.60 mmol, 4.0 eq.) were added and stirred under reflux for 24 hours. 111 mg of ammonium chloride (2.08 mmol, 1.26 eq.) and 377 μL of 100% acetic acid (6.60 mmol, 4.0 eq.) were added and stirred under reflux for 24 hours again. The mixture was concentrated under vacuo. The residue was suspended in acetonitrile and filtered off two times. The filter cakes were dissolved in DCM/methanol 1:1 and filtered over a silica column to provide 313 mg (1.19 mmol, 72.6%) of analytically pure target compound.
CN(C)c1cc(C(=N)N)nn1Cc1ccccc1F
Cl
[NH4+]
[Cl-]
CN(C)c1cc(C#N)nn1Cc1ccccc1F
C[O-].[Na+].[CH3:4][N:5]([CH3:21])[C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[N:9]=[C:8]([C:19]#[N:20])[CH:7]=1.[Cl-:22].[NH4+:23].C(O)(=O)C>CO>[ClH:22].[CH3:4][N:5]([CH3:21])[C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[N:9]=[C:8]([C:19](=[NH:23])[NH2:20])[CH:7]=1
1
CO
CC(=O)O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
839,323
CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2NC1=O
null
null
null
ord_dataset-074f86301ec5441ab3b52d902ac06949
2008-01-01T00:09:00
true
The title compound was prepared from (S)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril (prepared in Example 5) by the procedures described for the preparation of (R)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril (Example 5) from (R)-3-t-butyloxycarbonylamino-3,4-dihydrocarbostyril. HPLC/MS [M+H]+, 340; [M+Na]+, 362.
O=C(N[C@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
O=C(N[C@@H]1Cc2ccccc2NC1=O)c1cc2cc(Cl)ccc2[nH]1
null
null
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]1[CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][C:15]1=[O:24])=[O:12])=[CH:5]2.C(OC(N[C@@H]1CC2C(=CC=CC=2)NC1=O)=O)(C)(C)C>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@H:14]1[CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][C:15]1=[O:24])=[O:12])=[CH:5]2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
267,072
null
null
null
null
ord_dataset-134cf2fa32ab464880d75db06c38f35a
1993-01-01T00:05:00
true
According to the procedure of Example 22C, 1-(4'-hydroxy-3',5'-dimethoxyphenyl)-1-hexene-3,5-dione is reacted with t-butylchlorodimethyl silane to afford 1-(4'-t-butyldimethylsilyloxy-3',5'-dimethoxyphenyl)-1-hexene-3,5-dione suitably pure for further use.
COc1cc(C=CC(=O)CC(C)=O)cc(OC)c1O[Si](C)(C)C(C)(C)C
null
COc1cc(C=CC(=O)CC(C)=O)cc(OC)c1O
CC(C)(C)[Si](C)(C)Cl
null
[OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([CH:10]=[CH:11][C:12](=[O:17])[CH2:13][C:14](=[O:16])[CH3:15])=[CH:4][C:3]=1[O:18][CH3:19].[C:20]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])([CH3:22])[CH3:21]>>[Si:24]([O:1][C:2]1[C:3]([O:18][CH3:19])=[CH:4][C:5]([CH:10]=[CH:11][C:12](=[O:17])[CH2:13][C:14](=[O:16])[CH3:15])=[CH:6][C:7]=1[O:8][CH3:9])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:26])[CH3:25]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
367,832
null
null
null
null
ord_dataset-b18df02d6e9345faa0f2dae281a0870a
1997-01-01T00:06:00
true
Phthalic acid anhydride (15.1 g, 102 mmol) and 4-amino phenyl acetic acid (15.2 g, 102 mmol) were dissolved in acetic acid and heated at reflux for 1 hour. Upon cooling on an ice bath, the product crystallized. The solid was filtered off, washed with water, and dried under vacuum overnight. The yield of the title compound was 24.1 g (86%) as an off white solid.
O=C(O)Cc1ccc(N2C(=O)c3ccccc3C2=O)cc1
null
Nc1ccc(CC(=O)O)cc1
O=C1OC(=O)c2ccccc21
null
[C:1]1(=[O:11])[O:6][C:4](=O)[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([OH:22])=[O:21])=[CH:15][CH:14]=1>C(O)(=O)C>[O:11]=[C:1]1[C:2]2[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:6])[N:12]1[C:13]1[CH:14]=[CH:15][C:16]([CH2:19][C:20]([OH:22])=[O:21])=[CH:17][CH:18]=1
null
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
76,479
null
null
null
null
ord_dataset-8868acadaee548d5802e504148fc3b63
1981-01-01T00:01:00
true
To a stirred mixture of dry pyridine (15 ml) and dry methylene chloride (225 ml), chromic anhydride (9.0 g) is added in one portion, and the mixture is stirred for 15 minutes. A solution of 3-methylamino-4-phenoxy-5-sulfamylbenzyl alcohol (4.6 g; prepared as described in Example 5) in acetone (25 ml) is then added in one portion and the mixture is stirred for a further 15 minutes. The resulting inorganic precipitate is removed by filtration and the filtrate is evaporated in vacuo. The residue is extracted with diethyl ether (300 ml) and filtered to remove a small amount of insoluble material. The diethyl ether is removed in vacuo to yield crude 3-methylamino-4-phenoxy-5-sulfamylbenzaldehyde. After recrystallization from ethanol it is obtained with a melting point of 166°-167° C.
CNc1cc(C=O)cc(S(N)(=O)=O)c1Oc1ccccc1
null
CNc1cc(CO)cc(S(N)(=O)=O)c1Oc1ccccc1
null
null
N1C=CC=CC=1.C(Cl)Cl.[CH3:10][NH:11][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([S:27](=[O:30])(=[O:29])[NH2:28])[C:19]=1[O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:15][OH:16]>CC(C)=O>[CH3:10][NH:11][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([S:27](=[O:30])(=[O:29])[NH2:28])[C:19]=1[O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:15]=[O:16]
0.25
ClCCl
CC(C)=O
c1ccncc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,600,305
Cl[Ru](Cl)Cl
[Na+]
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
A solution of (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5-oxide (7.24 g, 17.2 mmol) and sodium periodate (4.04 g, 18.9 mmol) in a mixture of ethyl acetate (60 ml), acetonitrile (60 ml) and cold water (99.6 ml) was treated with ruthenium(III) chloride (35.6 mg, 172 μmol). The reaction mixture was stirred at 23° C. for 30 minutes. For the workup, the reaction mixture was extracted with a saturated solution of sodium hydrogencarbonate, the aqueous layer re-extracted with ethyl acetate, and the combined organic layers were dried over sodium sulphate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of heptane and ethyl acetate=100:0 to 0:100 as the eluent. The (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5,5-dioxide (4.1 g, 55% yield) was obtained as a light yellow solid. MS (ISP): m/z=460.2 [M+Na]+.
COc1ccc(CN2[C@](C)(c3ccccc3F)[C@H]3COC[C@H]3OS2(=O)=O)c(OC)c1
null
COc1ccc(CN2S(=O)O[C@@H]3COC[C@@H]3[C@@]2(C)c2ccccc2F)c(OC)c1
[O-][I+3]([O-])([O-])[O-]
null
[CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]1[C@@:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])([CH3:15])[C@@H:13]2[C@@H:9]([CH2:10][O:11][CH2:12]2)[O:8][S:7]1=[O:23].I([O-])(=O)(=O)=[O:31].[Na+].C(#N)C.O>C(OCC)(=O)C.[Ru](Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]1[C@@:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[F:22])([CH3:15])[C@@H:13]2[C@@H:9]([CH2:10][O:11][CH2:12]2)[O:8][S:7]1(=[O:31])=[O:23]
0.5
CCOC(C)=O
CC#N
O
23
54.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
242,810
[Pd]
null
null
null
ord_dataset-fa3b512e2d924b9b965301ebcba6853d
1992-01-01T00:03:00
true
To a solution of (2R,4R)-1-p-nitrobenzyloxycarbonyl-2-(2-methylaminocarbonylethyl)-4-hydroxypyrrolidine (1.52 g) in tetrahydrofuran (15 ml) and ethanol (15 ml), 10 palladium-carbon (228 mg) was added. The mixture was stirred at room temperature for 3.5 hours under an atmospheric pressure of hydrogen. The reaction mixture was filtered to remove the catalyst. The filtrate was concentrated, and the residue was combined with water, washed with dichloromethane and lyophilized to give (2R,4R)-2-(2-methylaminocarbonylethyl)-4-hydroxypyrrolidine.
CNC(=O)CC[C@@H]1C[C@@H](O)CN1
null
CNC(=O)CC[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1
[H][H]
null
[N+](C1C=CC(COC([N:12]2[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]2[CH2:18][CH2:19][C:20]([NH:22][CH3:23])=[O:21])=O)=CC=1)([O-])=O.[H][H]>O1CCCC1.C(O)C.[C].[Pd]>[CH3:23][NH:22][C:20]([CH2:19][CH2:18][C@@H:13]1[CH2:14][C@@H:15]([OH:17])[CH2:16][NH:12]1)=[O:21]
null
C1CCOC1
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
440,713
NN
null
null
null
ord_dataset-3e8f24b5bc8e4d8bb9b6e7e89a956e12
1999-01-01T00:09:00
true
The compound was prepared in a manner analogous to the preparation of the compound of Example 48 from the compound of Example 50 (830 mg, 1 .54 mmol) and hydrazine monohydrate (0.23 ml, 4.62 mmol) to give the title compound (63 mg) as a white solid m.p. 161-162°. MS m/z 411 (M+H)+.
COc1cc(Nc2nccc(-c3ccc(OCCCN)cc3)n2)cc(OC)c1OC
null
COc1cc(Nc2nccc(-c3ccc(OCCCN4C(=O)c5ccccc5C4=O)cc3)n2)cc(OC)c1OC
null
null
C1(=O)[N:5]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]4[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=4)[N:17]=3)=[CH:12][CH:11]=2)C(=O)C2=CC=CC=C12.O.NN>>[NH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]3[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=3)[N:17]=2)=[CH:12][CH:11]=1
null
O
null
null
null
28.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
735,607
O=C([O-])[O-]
[K+]
null
null
ord_dataset-76dd1b78ee414d2da0ed30700ef026f7
2006-01-01T00:10:00
true
N-{(1R,2R)-1-[(2-Acetoxyacetyl)amino]-2,3-dihydro-1H-inden-2-yl}-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Example 6; 632 mg, 1.36 mmol) was dissolved in THF (10 mL), MeOH (10 mL) and K2CO3 (100 mg) were then added and the suspension stirred at ambient temperature for 16 hours. Water (50 mL) was added and the aqueous phase was extracted with EtOAc (3×30 mL). The combined organic phases were washed with water (2×50 mL), brine (50 mL) and dried (MgSO4). The solvent was removed by evaporation under reduced pressure, the crude product was triturated (EtOAc:isohexane, 1:10), filtered, washed with isohexane (5 mL) and dried to give the title compound (428 mg, 74%) as a white solid.
O=C(CO)N[C@@H]1c2ccccc2C[C@H]1NC(=O)c1cc2sc(Cl)c(Cl)c2[nH]1
null
CC(=O)OCC(=O)N[C@@H]1c2ccccc2C[C@H]1NC(=O)c1cc2sc(Cl)c(Cl)c2[nH]1
null
null
C([O:4][CH2:5][C:6]([NH:8][C@@H:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]1[NH:18][C:19]([C:21]1[NH:25][C:24]2[C:26]([Cl:30])=[C:27]([Cl:29])[S:28][C:23]=2[CH:22]=1)=[O:20])=[O:7])(=O)C.CO.C([O-])([O-])=O.[K+].[K+].O>C1COCC1>[Cl:29][C:27]1[S:28][C:23]2[CH:22]=[C:21]([C:19]([NH:18][C@@H:10]3[CH2:11][C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C@H:9]3[NH:8][C:6](=[O:7])[CH2:5][OH:4])=[O:20])[NH:25][C:24]=2[C:26]=1[Cl:30]
16
O
CO
C1CCOC1
25
74.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,475,036
null
null
null
null
ord_dataset-c3c1091f873b4f40827973a6f1f9b685
2014-01-01T00:09:00
true
The title compound is prepared from N-(1-cyano-piperidin-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide and N-hydroxy-tetrahydro-pyran-4-carboxamidine following a procedure analogous to that described in Example 1. LC (method 1): tR=1.10 min; Mass spectrum (ESI+): m/z=464 [M+H]+.
O=C(c1ccc(-c2cnco2)cc1)N(C1CC1)C1CCN(c2nc(C3CCOCC3)no2)CC1
null
N#CN1CCC(N(C(=O)c2ccc(-c3cnco3)cc2)C2CC2)CC1
N=C(NO)C1CCOCC1
null
[C:1]([N:3]1[CH2:8][CH2:7][CH:6]([N:9]([CH:23]2[CH2:25][CH2:24]2)[C:10](=[O:22])[C:11]2[CH:16]=[CH:15][C:14]([C:17]3[O:21][CH:20]=[N:19][CH:18]=3)=[CH:13][CH:12]=2)[CH2:5][CH2:4]1)#[N:2].[OH:26][NH:27][C:28]([CH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=N>>[CH:23]1([N:9]([CH:6]2[CH2:5][CH2:4][N:3]([C:1]3[O:26][N:27]=[C:28]([CH:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[N:2]=3)[CH2:8][CH2:7]2)[C:10](=[O:22])[C:11]2[CH:12]=[CH:13][C:14]([C:17]3[O:21][CH:20]=[N:19][CH:18]=3)=[CH:15][CH:16]=2)[CH2:25][CH2:24]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
271,909
Cl
null
null
null
ord_dataset-347c0709d28a44dea43ca42052be4db3
1993-01-01T00:07:00
true
To a solution of 4.9 g of cyclohexylamine and 5.4 g of triethylamine in 100 ml of methylenechloride, was added 5.8 g of 1,4-phenylenedipropionyl chloride under ice cooling with stirring. Stirring was continued for 3 hours at room temperature, and 500 ml of water was added to the reaction solution. Conc.-HCl was added to the mixture until aqueous layer became weak-acidic. The solid material precipitated was collected by filtration, washed with methylenechloride and water in that order, and dried, giving 7.4 g of N,N'-dicyclohexyl-1,4-phenylenedipropionamide.
O=C(CCc1ccc(CCC(=O)NC2CCCCC2)cc1)NC1CCCCC1
null
NC1CCCCC1
CCN(CC)CC
O=C(Cl)CCc1ccc(CCC(=O)Cl)cc1
[CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([N:10]([CH2:13][CH3:14])CC)C.[C:15]1([CH2:26][CH2:27][C:28](Cl)=[O:29])[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23](Cl)=[O:24])=[CH:17][CH:16]=1.Cl>C(Cl)Cl.O>[CH:1]1([NH:7][C:28](=[O:29])[CH2:27][CH2:26][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23]([NH:10][CH:13]3[CH2:14][CH2:3][CH2:2][CH2:1][CH2:6]3)=[O:24])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
3
O
ClCCl
null
null
null
86
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,053,493
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=P([O-])([O-])[O-]
[K+]
null
ord_dataset-373415d3e0e54004837cf4831e67666f
2011-01-01T00:05:00
true
Degassed N,N-dimethylformamide (0.37 mL) was added to 3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol (Example 29; 30.6 mg, 0.0621 mmol), (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 21.1 mg, 0.0917 mmol), tetrakis(triphenylphosphine)palladium (0) (9.0 mg, 0.0078 mmol) and potassium phosphate (29.4 mg, 0.138 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 85 to 94° C. for three hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=1/1) to give the title compound (29.5 mg, 92%).
CCC(O)(CC)CCc1ccc(C(CC)(CC)c2ccc(-c3cncc(CC(=O)OC)c3)c(C)c2)cc1C
null
CCC(O)(CC)CCc1ccc(C(CC)(CC)c2ccc(B3OC(C)(C)C(C)(C)O3)c(C)c2)cc1C
COC(=O)Cc1cncc(Br)c1
null
[CH2:1]([C:3]([OH:36])([CH2:34][CH3:35])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH2:31][CH3:32])([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[C:17]([CH3:30])[CH:16]=2)[CH2:13][CH3:14])=[CH:8][C:7]=1[CH3:33])[CH3:2].[CH3:37][O:38][C:39](=[O:48])[CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[C:45](Br)[CH:46]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:37][O:38][C:39](=[O:48])[CH2:40][C:41]1[CH:42]=[N:43][CH:44]=[C:45]([C:18]2[CH:19]=[CH:20][C:15]([C:12]([CH2:13][CH3:14])([C:9]3[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([CH2:34][CH3:35])([OH:36])[CH2:1][CH3:2])=[C:7]([CH3:33])[CH:8]=3)[CH2:31][CH3:32])=[CH:16][C:17]=2[CH3:30])[CH:46]=1
3
O
null
null
89.5
92.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
547,043
null
null
null
null
ord_dataset-d31180f42ced44719fd9e72685c798bf
2002-01-01T00:05:00
true
A solution of 3.1 g (99 mmol) of 4-formylbenzonitrile (commercially available) and 40 g (120 mmol) of (triphenylphosphoranylidene)crotonaldehyde [prepared as described in Tetrahedron Lett., 493 (1971)] in 200 ml of dichloromethane was stirred at ambient temperature overnight. At the end of this time, the reaction mixture was concentrated to dryness in vacuo. The resulting residue was purified by chromatography on a silica gel (250 g) column using ethyl acetate as the eluant to give a mixture of the desired compound and a Geometrical isomer thereof. A solution of the mixture of the two isomers in 150 ml of toluene was heated at reflux under irradiation with a tungsten lamp (300 W) for 12 hours. The reaction mixture was then concentrated in vacuo. The resulting residue was purified by chromatography on a silica gel (1.2 kg) column using a 1:9 mixture of ethyl acetate and toluene as the eluant to afford 3.46 g (yield 19%) of the title compound as pale brown needle-like crystals which were collected by filtration.
N#Cc1ccc(/C=C/C=C/C=O)cc1
null
O=C/C=C/C=P(c1ccccc1)(c1ccccc1)c1ccccc1
N#Cc1ccc(C=O)cc1
null
[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)=O.C1(P(=[CH:30]/[CH:31]=[CH:32]/[CH:33]=[O:34])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[O:34]=[CH:33]/[CH:32]=[CH:31]/[CH:30]=[CH:1]/[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1
null
ClCCl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,743,677
[H-]
[Na+]
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
To a stirred solution of 2-methyl-N-(7H-purin-6-yl)propanamide (1.5 g, 24.36 mmol) in dimethylformamide (20 mL), sodium hydride (0.88 g, 36.55 mmol) was added portion wise in 10 minutes at 0° C. The above suspension was stirred for 10 minutes at 0° C. followed by addition of 2-(trimethylsilyl)ethoxymethyl chloride (4.87 g, 29.24 mmol) slowly at 0° C. under nitrogen atmosphere. The reaction was stirred at room temperature for 16 h. After completion of the reaction, the mixture was quenched with saturated aqueous solution of ammonium chloride and product was extracted with dichloromethane (2×50 mL). The organics were then separated, dried (magnesium sulfate) and concentrated to dryness under vacuum and the crude was purified by flash chromatography eluting with 2% methanol in dichloromethane. Concentration of the desired fractions afford 2-methyl-N-[7-(2-trimethylsilylethoxymethyl)purin-6-yl]propanamide (2) as white solid. Yield: 2 g, 24%.
CC(C)C(=O)Nc1ncnc2ncn(COCC[Si](C)(C)C)c12
null
C[Si](C)(C)CCOCCl
CC(C)C(=O)Nc1ncnc2nc[nH]c12
null
[CH3:1][CH:2]([CH3:15])[C:3]([NH:5][C:6]1[N:14]=[CH:13][N:12]=[C:11]2[C:7]=1[NH:8][CH:9]=[N:10]2)=[O:4].[H-].[Na+].[CH3:18][Si:19]([CH3:26])([CH3:25])[CH2:20][CH2:21][O:22][CH2:23]Cl>CN(C)C=O>[CH3:18][Si:19]([CH3:26])([CH3:25])[CH2:20][CH2:21][O:22][CH2:23][N:8]1[C:7]2[C:11](=[N:12][CH:13]=[N:14][C:6]=2[NH:5][C:3](=[O:4])[CH:2]([CH3:15])[CH3:1])[N:10]=[CH:9]1
0.17
CN(C)C=O
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
221,547
null
null
null
null
ord_dataset-42629b4cf1094978a5e5f29f22639ee7
1991-01-01T00:01:00
true
A mixture of 2.9 g of 3-(2-chlorophenyl)-1,2,4-thiadiazole-5-sulfonamide in 11 ml of trimethyl orthoisobutyrate was warmed to about 85° with an oil bath. After 2.5 hours the solution was cooled to room temperature, whereupon a precipitate formed. Hexane (25 ml) was added to insure complete precipitation. The solid was filtered, washed with hexane and vacuum dried (P2O5) to give 3.08 g of solid, m.p. 75°-76°.
COC(=NS(=O)(=O)c1nc(-c2ccccc2Cl)ns1)C(C)C
null
NS(=O)(=O)c1nc(-c2ccccc2Cl)ns1
COC(OC)(OC)C(C)C
null
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[C:11]([S:13]([NH2:16])(=[O:15])=[O:14])[S:10][N:9]=1.CCCCCC.[C:23](OC)(OC)([O:27][CH3:28])[CH:24]([CH3:26])[CH3:25]>>[CH3:28][O:27][C:23](=[N:16][S:13]([C:11]1[S:10][N:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[N:12]=1)(=[O:14])=[O:15])[CH:24]([CH3:26])[CH3:25]
null
CCCCCC
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
860,932
F[N+]12CC[N+](CCl)(CC1)CC2
null
null
null
ord_dataset-93908aaae836460ebd48d733eccad483
2009-01-01T00:01:00
true
The product of Example 3 (0.1 g) was dissolved in methanol (10 ml), Selectfluor™ (0.12 g) added and stirred for 20 h. The mixture was evaporated and purified by silica gel chromatography (5% methanol/DCM) to yield the title product as a white solid. Yield 19 mg.
C[C@H](CO)Nc1nc(SCc2cccc(Cl)c2)nc(O)c1F
null
F[B-](F)(F)F
C[C@H](CO)Nc1cc(O)nc(SCc2cccc(Cl)c2)n1
null
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][S:6][C:7]1[N:12]=[C:11]([OH:13])[CH:10]=[C:9]([NH:14][C@H:15]([CH3:18])[CH2:16][OH:17])[N:8]=1.[B-](F)(F)(F)[F:23].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][S:6][C:7]1[N:12]=[C:11]([OH:13])[C:10]([F:23])=[C:9]([NH:14][C@H:15]([CH3:18])[CH2:16][OH:17])[N:8]=1
20
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,200,237
[Na+]
[OH-]
null
null
ord_dataset-fb72428f30234761b4216139dc228d0c
2012-01-01T00:09:00
true
A solution of N-[4-(2-Methyl-2,3,4,9-tetrahydro-1H-β-carbolin-6-ylsulfamoyl)-phenyl]-acetamide (example 7) (80 mg, 0.2 mmol) in 1 mL of an aqueous 10% de NaOH solution was refluxed for 2 h. The resulting mixture was treated with H2O (25 mL) and EtOAc (25 mL) and neutralized by addition of AcOH glacial. The aqueous phase was washed again with EtOAc and the combined organic extracts dried to afford 50 mg of 4-amino-N-(2-methyl-2,3,4,9-tetrahydro-1H-β-carbolin-6-yl)-benzenesulfonamide as a cream colored amorphous solid, mp 236-237° C. 1H-NMR (300 MHz, DMSO-d6): (ppm) 2.36 (s, 3H); 2.55 (bb, 2H); 2.61 (bb, 2H); 3.45 (bb, 2H); 5.83 (bb, 2H); 6.44 (sys AB, 2H, J=8.7 Hz); 6.68 (dd, 1H, J=8.4, 1.8 Hz); 6.99 (bb, 1H); 7.05 (d, 1H, J=8.4 Hz); 7.25 (sys AB, 2H, J=8.7 Hz); 9.27 (s, 1H); 10.63 (s, 1H).
CN1CCc2c([nH]c3ccc(NS(=O)(=O)c4ccc(N)cc4)cc23)C1
null
CC(=O)Nc1ccc(S(=O)(=O)Nc2ccc3[nH]c4c(c3c2)CCN(C)C4)cc1
null
null
[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([NH:15][S:16]([C:19]4[CH:24]=[CH:23][C:22]([NH:25]C(=O)C)=[CH:21][CH:20]=4)(=[O:18])=[O:17])[CH:10]=3)[NH:5][C:4]=2[CH2:3]1.[OH-].[Na+].O.CCOC(C)=O>CC(O)=O>[NH2:25][C:22]1[CH:23]=[CH:24][C:19]([S:16]([NH:15][C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[NH:5][C:4]2[CH2:3][N:2]([CH3:1])[CH2:14][CH2:13][C:12]3=2)(=[O:18])=[O:17])=[CH:20][CH:21]=1
null
O
CCOC(C)=O
CC(=O)O
null
70.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,724,592
null
null
null
null
ord_dataset-36057d699ac5449e9c37eb99abf78b03
2016-01-01T00:05:00
true
(S)-4-benzyl-3-methyl-5-oxomorpholine-3-carboxylic acid (2.49 g, 10 mmol) was reacted with benzyl bromide (2.05 g, 12 mmol) according to the procedure as described in Example 34, Step A to give the title compound as colorless oil (2.38 g, 70%). The compound was characterized by the following spectroscopic data:
C[C@@]1(C(=O)OCc2ccccc2)COCC(=O)N1Cc1ccccc1
null
C[C@@]1(C(=O)O)COCC(=O)N1Cc1ccccc1
BrCc1ccccc1
null
[CH2:1]([N:8]1[C:13](=[O:14])[CH2:12][O:11][CH2:10][C@@:9]1([CH3:18])[C:15]([OH:17])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:1]([N:8]1[C:13](=[O:14])[CH2:12][O:11][CH2:10][C@@:9]1([CH3:18])[C:15]([O:17][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
null
null
null
null
null
null
70.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
821,767
null
null
null
null
ord_dataset-ec58fad8331a42c5a67ad75aac6713b4
2008-01-01T00:05:00
true
The title compound, MS: m/e=480.2 (M+H+), was prepared in analogy to example 16 from 7-amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one and N-(3,5-difluoro-benzyl)-2-methoxy-malonamic acid.
COC(C(=O)NCc1cc(F)cc(F)c1)C(=O)NC1C(=O)N(C)c2ccccc2-c2ccccc21
null
CN1C(=O)C(N)c2ccccc2-c2ccccc21
COC(C(=O)O)C(=O)NCc1cc(F)cc(F)c1
null
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2.[F:19][C:20]1[CH:21]=[C:22]([CH:33]=[C:34]([F:36])[CH:35]=1)[CH2:23][NH:24][C:25](=[O:32])[CH:26]([O:30][CH3:31])[C:27](O)=[O:28]>>[F:19][C:20]1[CH:21]=[C:22]([CH:33]=[C:34]([F:36])[CH:35]=1)[CH2:23][NH:24][C:25](=[O:32])[CH:26]([O:30][CH3:31])[C:27]([NH:1][CH:2]1[C:8](=[O:9])[N:7]([CH3:10])[C:6]2[CH:11]=[CH:12][CH:13]=[CH:14][C:5]=2[C:4]2[CH:15]=[CH:16][CH:17]=[CH:18][C:3]1=2)=[O:28]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,529,529
null
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
A mixture of ethyl 2-[(2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate (4 g) and N-[4-(prop-2-en-1-yloxy)cyclohexyl]-4H-1,2,4-triazol-3-amine (1.3 g) was stirred at 250° C. for 20 min under microwave irradiation. The obtained reaction mixture was purified by silica gel column chromatography to give the title compound as a colorless solid (0.7 g, 24%).
C=CCOC1CCC(n2c(=O)c(Cc3ccc(-c4ccccc4C#N)cc3)c(CCC)n3ncnc23)CC1
null
C=CCOC1CCC(Nc2nnc[nH]2)CC1
CCCC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OCC
null
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([C:22](=O)[CH2:23][CH2:24][CH3:25])[C:17](OCC)=[O:18])=[CH:11][CH:10]=1)#[N:2].[CH2:27]([O:30][CH:31]1[CH2:36][CH2:35][CH:34]([NH:37][C:38]2[NH:42][CH:41]=[N:40][N:39]=2)[CH2:33][CH2:32]1)[CH:28]=[CH2:29]>>[O:18]=[C:17]1[C:16]([CH2:15][C:12]2[CH:13]=[CH:14][C:9]([C:4]3[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=3)=[CH:10][CH:11]=2)=[C:22]([CH2:23][CH2:24][CH3:25])[N:39]2[N:40]=[CH:41][N:42]=[C:38]2[N:37]1[CH:34]1[CH2:33][CH2:32][CH:31]([O:30][CH2:27][CH:28]=[CH2:29])[CH2:36][CH2:35]1
0.33
null
null
null
250
null
23.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
174,588
null
null
null
null
ord_dataset-4937da99a6a247eb90fa70f0d2eac3db
1988-01-01T00:07:00
true
A mixture of 5.3 g (0.03 mole) of 1-(chloromethyl)naphthalene and 8.6556 g (0.033 mole) of triphenylphosphine in 150 mL of dimethylformamide was heated at reflux with stirring for 5 hours. A copious white precipitate formed. The precipitate was filtered and washed with 100 mL of dimethylformamide and 100 mL of ether. The product was dried in vacuo to yield 11.97 g (91%) of 1-naphthylmethyltriphenylphosphonium chloride as white crystals: mp 285°-288°; IR (KBr) 3050, 3010, 2880, 2790, 1665, 1590, 1510, 1485, 1440, 1385, 1335, 1275, 1155, 1110, 1095, 875, 810, 785, 730, and 690 cm-1 ; NMR (DMSO) δ5.67 (d, J=15 Hz, 2H), 7.60 (m, 15H) and 7.73 (m, 7H).
[Cl-]
c1ccc([P+](Cc2cccc3ccccc23)(c2ccccc2)c2ccccc2)cc1
c1ccc(P(c2ccccc2)c2ccccc2)cc1
ClCc1cccc2ccccc12
null
[Cl:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[C:13]1([P:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C)C=O>[Cl-:1].[C:3]1([CH2:2][P+:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1
5
CN(C)C=O
null
null
null
90.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,466,879
O=S(=O)(O)O
[K+]
null
null
ord_dataset-fd1fa959d6264608b0b7fcda16741bfd
2014-01-01T00:08:00
true
1-(2-tert-butylphenyl)pyrrolidine (350 mg, 1.72 mmol) was added portionwise to conc. H2SO4 (1 mL) to generate a yellow homogeneous solution. The solution was then cooled to 0° C. and KNO3 (191 mg, 1.9 mmol) was added portionwise maintaining the internal temperature below 5° C. The reaction was stirred for 2 h and then poured on ice-water and extracted with DCM, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography to obtain 1-(2-tert-butyl-5-nitrophenyl)pyrrolidine (325 mg, 76%). LC/MS: m/z 248.9 (M+H)+ at 2.39 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
CC(C)(C)c1ccc([N+](=O)[O-])cc1N1CCCC1
null
CC(C)(C)c1ccccc1N1CCCC1
O=[N+]([O-])[O-]
null
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].OS(O)(=O)=O.[N+:21]([O-])([O-:23])=[O:22].[K+]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N+:21]([O-:23])=[O:22])=[CH:7][C:6]=1[N:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]
2
null
null
null
0
76.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,391,068
null
null
null
null
ord_dataset-31641fb65b34430fa7435229b949b604
2014-01-01T00:01:00
true
The title compound was prepared in the same manner as described for intermediate 61 using ethyl 4-[4-(methylthio)phenyl]-2,4-dioxobutanoate (851 mg, 3.20 mmol), benzene (6 mL), 1-(1-methylethyl)-1H-pyrazol-5-amine (400 mg, 3.20 mmol), and acetic acid (3 mL). The crude product was purified by column chromatography (Silica gel, eluent; 0 to 100% EtOAc/hexanes) to give 870 mg (63%) of product. LCMS E-S (M+H)=433.2. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.47-1.57 (m, 3H), 1.66 (d, J=6.8 Hz, 6H), 2.58 (s, 3H), 4.56 (q, J=7.2 Hz, 2H), 5.38-5.55 (m, 1H), 7.36-7.46 (m, 2H), 8.12-8.19 (m, 2H), 8.22 (s, 1H), 8.40 (s, 1H).
CCOC(=O)c1cc(-c2ccc(SC)cc2)nc2c1cnn2C(C)C
null
CCOC(=O)C(=O)CC(=O)c1ccc(SC)cc1
CC(C)n1nccc1N
null
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][C:11](=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:5][CH:4]=1.C1C=CC=CC=1.[CH3:25][CH:26]([N:28]1[C:32]([NH2:33])=[CH:31][CH:30]=[N:29]1)[CH3:27]>C(O)(=O)C>[CH3:25][CH:26]([N:28]1[C:32]2[N:33]=[C:9]([C:6]3[CH:7]=[CH:8][C:3]([S:2][CH3:1])=[CH:4][CH:5]=3)[CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:31]=2[CH:30]=[N:29]1)[CH3:27]
null
c1ccccc1
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,241,583
Cl
null
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
3-Chloro-6-(1-isopropylpiperidin-4-yl)pyridazine, hydrochloride (0.5 g, 1.6 mmol) and 2-methylpyridin boronic acid (0.241 g, 1.76 mmol) were mixed with catalyst and reacted in the same manner as in example 18. The title compound was isolated as white crystals of the trihydrochloride. Yield: 164 mg (25%).
Cc1cc(-c2ccc(C3CCN(C(C)C)CC3)nn2)ccn1
null
CC(C)N1CCC(c2ccc(Cl)nn2)CC1
CC1(B(O)O)C=CC=CN1
null
[ClH:1].[Cl:2][C:3]1[N:4]=[N:5][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]([CH3:17])[CH3:16])[CH2:11][CH2:10]2)=[CH:7][CH:8]=1.[CH3:18][C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][NH:20]1>>[ClH:2].[ClH:1].[ClH:2].[CH:15]([N:12]1[CH2:13][CH2:14][CH:9]([C:6]2[N:5]=[N:4][C:3]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([CH3:18])[CH:24]=3)=[CH:8][CH:7]=2)[CH2:10][CH2:11]1)([CH3:17])[CH3:16]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,648,109
null
null
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
The title compound was synthesized from 1-methyl-7-hydroxy-β-carboline (1.504 g, 4.770 mmol) in presence of 1-bromo-3-methylbutane (1.440 g, 9.520 mmol) as described here above.
Cc1nccc2c3ccc(OCCC(C)C)cc3n(CCC(C)C)c12
null
CC(C)CCBr
Cc1nccc2c1[nH]c1cc(O)ccc12
null
[CH3:1][C:2]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[C:10]([OH:15])[CH:11]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1.Br[CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20]>>[CH3:1][C:2]1[C:14]2[N:13]([CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH2:4][CH2:5][CH:6]([CH3:7])[CH3:14])[CH:11]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1
null
null
null
null
null
null
69
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,220,508
[Pd]
null
null
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
To a solution of spiro[5.5]undec-1-en-3-one (8.9 g) obtained in Step 1 in tetrahydrofuran (360 mL) was added 5% palladium carbon (0.89 g), followed by stirring the reaction mixture at room temperature in an atmosphere of hydrogen under normal pressure for 2 hours. Then, the reaction mixture was filtered through Celite and the filtrate was concentrated to obtain spiro[5.5]undecan-3-one (9.3 g).
O=C1CCC2(CCCCC2)CC1
null
O=C1C=CC2(CCCCC2)CC1
[H][H]
null
[CH:1]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][C:3](=[O:12])[CH:2]=1.[H][H]>O1CCCC1.[C].[Pd]>[CH2:5]1[C:6]2([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:1][CH2:2][C:3](=[O:12])[CH2:4]1
null
C1CCOC1
null
null
null
null
103.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,730,923
[Pd]
null
null
null
ord_dataset-36057d699ac5449e9c37eb99abf78b03
2016-01-01T00:05:00
true
10% Pd/C (1.19 g) was added to a solution of compound 30 (3.97 g, 5.91 mmol) in ethanol (100 mL). The resulting mixture was stirred under H2 (g) atmosphere at room temperature for 12 hours. The reaction mixture was filtered through a celite pad and washed with ethanol (2×20 mL). The combined filtrate was evaporated in vacuo to give an oily residue which was triturated with Et2O to provide an off-white solid 28 (2.67 g, 98% yield).
Nc1ccc(CC2CN3CCCN(CC(=O)O)CCN(CCCN(CC(=O)O)CC3)C2)cc1
null
O=C(CN1CCCN2CCN(CC(=O)OCc3ccccc3)CCCN(CC1)CC(Cc1ccc([N+](=O)[O-])cc1)C2)OCc1ccccc1
null
null
C([O:8][C:9]([CH2:11][N:12]1[CH2:25][CH2:24][CH2:23][N:22]2[CH2:26][CH:27]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([N+:36]([O-])=O)=[CH:32][CH:31]=3)[CH2:28][N:15]([CH2:16][CH2:17][CH2:18][N:19]([CH2:39][C:40]([O:42]CC3C=CC=CC=3)=[O:41])[CH2:20][CH2:21]2)[CH2:14][CH2:13]1)=[O:10])C1C=CC=CC=1>C(O)C.[Pd]>[C:9]([CH2:11][N:12]1[CH2:25][CH2:24][CH2:23][N:22]2[CH2:26][CH:27]([CH2:29][C:30]3[CH:31]=[CH:32][C:33]([NH2:36])=[CH:34][CH:35]=3)[CH2:28][N:15]([CH2:16][CH2:17][CH2:18][N:19]([CH2:39][C:40]([OH:42])=[O:41])[CH2:20][CH2:21]2)[CH2:14][CH2:13]1)([OH:10])=[O:8]
12
CCO
null
null
25
97.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
117,411
null
null
null
null
ord_dataset-3708161f4ba04e959b9a7a8d59fd86e1
1984-01-01T00:05:00
true
Finely ground N-isopropyl valine (31 mmol) in 150 ml dioxane is heated to 38°-40° and excess carbonyl chloride is slowly passed in over 4-5 hours. Dry air is then passed through the reaction for 18 hours, after which the dioxane is removed at 40° (20 mm) to yield 3,4-diisopropyl-oxazolidine-2,5-dione.
CC(C)C1C(=O)OC(=O)N1C(C)C
null
O=C(Cl)Cl
CC(C)N[C@H](C(=O)O)C(C)C
null
[CH:1]([NH:4][C@H:5]([C:9]([OH:11])=[O:10])[CH:6]([CH3:8])[CH3:7])([CH3:3])[CH3:2].[C:12](Cl)(Cl)=[O:13]>O1CCOCC1>[CH:1]([N:4]1[CH:5]([CH:6]([CH3:7])[CH3:8])[C:9](=[O:11])[O:10][C:12]1=[O:13])([CH3:2])[CH3:3]
null
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
722,307
Cl
null
null
null
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
2006-01-01T00:08:00
true
A mixture of methyl (2E)-3-[4-(9a-butyl-7-methoxy-3-oxo-2,3,9,9a-tetrahydro-1H-fluoren-4-yl)phenyl]-2-propenoate (60 mg, 92% weight pure, 0.128 mmol) and pyridine hydrochloride (741 mg, 6.41 mmol) was placed under a nitrogen atmosphere, heated in an oil bath at 190° C., and stirred. The reaction flask was periodically dipped deeper into the heating bath in order to melt the pyridine hydrochloride that condensed on the sides of the flask. After 2 hours at 190° C., the reaction mixture was cooled to room temperature and partitioned between EtOAc (10 mL) and water (10 mL). The aqueous phase was extracted with more EtOAc (2×5 mL). The combined EtOAc extracts were washed with brine, dried over MgSO4, filtered, and evaporated under vacuum to a yellow solid (55 mg). The crude product was suspended in EtOAc (10 mL) and extracted with 5% NaHCO3 (5 mL). The NaHCO3 solution was acidified with 2N HCl (2.5 mL) and extracted with EtOAc (2×5 mL). The latter EtOAc extracts were combined, washed with brine, dried over MgSO4, filtered, and evaporated under vacuum to a yellow solid (39.4 mg). This material was triturated with diethyl ether and dried under vacuum to afford (2E)-3-[4-(9a-butyl-7-hydroxy-3-oxo-2,3,9,9a-tetrahydro-1H-fluoren-4-yl)phenyl]-2-propenoic acid as a pale yellow solid.
CCCCC12CCC(=O)C(c3ccc(/C=C/C(=O)O)cc3)=C1c1ccc(O)cc1C2
null
CCCCC12CCC(=O)C(c3ccc(/C=C/C(=O)OC)cc3)=C1c1ccc(OC)cc1C2
null
null
[CH2:1]([C:5]12[CH2:17][CH2:16][C:15](=[O:18])[C:14]([C:19]3[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:27]([O:29]C)=[O:28])=[CH:21][CH:20]=3)=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:31]C)=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4].Cl.N1C=CC=CC=1>>[CH2:1]([C:5]12[CH2:17][CH2:16][C:15](=[O:18])[C:14]([C:19]3[CH:20]=[CH:21][C:22](/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28])=[CH:23][CH:24]=3)=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([OH:31])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4]
2
c1ccncc1
null
null
190
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,424,591
[Cl-]
[Na+]
null
null
ord_dataset-5e6956e6e8c24a168866a253f4a66c6c
2014-01-01T00:05:00
true
A mixture of dimethyl 2-(2-chloro-5-methoxy-4-nitrophenyl)malonate (3.0 g, 9.44 mmol) and sodium chloride (0.99 g, 16.99 mmol) in DMSO (50 mL) and water (0.17 mL, 9.44 mmol) was heated for 5 hours at 120° C. The reaction mass was allowed to cool to room temperature and water (400 mL) and EtOAc (50 mL) were added and stirring continued for 15 minutes. The separated aqueous layer was extracted with EtOAc (50 mL), and then the combined organic layers were washed with brine (50 mL), dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by column chromatography on neutral silica gel using 15-25% EtOAc in hexane to give the desired material (1.5 g, 61%) as a solid.
COC(=O)Cc1cc(OC)c([N+](=O)[O-])cc1Cl
null
COC(=O)C(C(=O)OC)c1cc(OC)c([N+](=O)[O-])cc1Cl
null
null
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH3:12])=[CH:4][C:3]=1[CH:13](C(OC)=O)[C:14]([O:16][CH3:17])=[O:15].[Cl-].[Na+].O.CCOC(C)=O>CS(C)=O>[CH3:17][O:16][C:14](=[O:15])[CH2:13][C:3]1[CH:4]=[C:5]([O:11][CH3:12])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[Cl:1]
0.25
CS(C)=O
CCOC(C)=O
O
120
61.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
198,787
C[O-]
[Na+]
null
null
ord_dataset-f6fafbb8ce5f4ef099be3a772075ec97
1989-01-01T00:10:00
true
34.7 g (0.469 mole) of ethyl formate are added dropwise with stirring to 129.4 g (0.469 mole) of 3,3-dimethyl-4-(4-trifluoromethylthiophenyl)-butan-2-one and 25.3 g (0.469 mole) of sodium methylate in 1 liter of diethyl ether at room temperature, and the mixture is stirred at room temperature for 4 hours after the addition is complete. For work-up, the mixture is extracted with 1 liter of water, and the combined aqueous extracts are washed once with diethyl ether, acidified to pH 1-2 with dilute aqueous hydrochloric acid and extracted with dichloromethane. The dichloromethane phase is dried over sodium sulphate and concentrated in vacuo. 90.5 g of 4,4-dimethyl-5-(4-trifluoromethylthiophenyl)-penten-1-ol-3-one are obtained; these are dissolved in 200 ml of methanol and 17.0 g (0.315 mol) of sodium methylate are added. Concentrating the solution in vacuo gives 97.1 g (75% of theory) of the sodium salt of 4,4-dimethyl-5-(4-trifluoromethylthiophenyl)-1 -penten-1-ol-3-one as a resin, which is further reacted without purification. ##STR875##
CC(C)(Cc1ccc(SC(F)(F)F)cc1)C(=O)C=CO
null
CC(=O)C(C)(C)Cc1ccc(SC(F)(F)F)cc1
CCOC=O
null
[CH:1](OCC)=[O:2].[CH3:6][C:7]([CH3:23])([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=1)[C:8](=[O:10])[CH3:9].C[O-].[Na+]>C(OCC)C>[CH3:6][C:7]([CH3:23])([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][C:19]([F:21])([F:22])[F:20])=[CH:14][CH:13]=1)[C:8](=[O:10])[CH:9]=[CH:1][OH:2]
4
CCOCC
null
null
25
63.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,641,976
Cl
null
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
To a solution of (1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol HCl (1.00 g, 5.44 mmol) and 2-amino-4,6-dichloropyrimidine (0.982 g, 5.99 mmol) in isopropyl alcohol (8 mL) was added Et3N (1.90 mL, 13.6 mmol). The reaction was heated to 90° C. for 1 h in an oil bath then cooled, filtered and concentrated in vacuo. The residue was dissolved in CH2Cl2 and purified by flash chromatography (20 to 50% MeOH/CH2Cl2) to afford the title compound as an off-white solid (2.025 g, >99%). LC/MS: Rt=0.81 min ES 260 (FA standard).
OC[C@H]1C[C@@H](Nc2cc(Cl)ncn2)[C@H](O)[C@@H]1O
null
Nc1nc(Cl)cc(Cl)n1
N[C@@H]1C[C@H](CO)[C@@H](O)[C@H]1O
null
Cl.[NH2:2][C@@H:3]1[CH2:7][C@H:6]([CH2:8][OH:9])[C@@H:5]([OH:10])[C@H:4]1[OH:11].N[C:13]1[N:18]=[C:17](Cl)[CH:16]=[C:15]([Cl:20])[N:14]=1.CCN(CC)CC>C(O)(C)C>[Cl:20][C:15]1[N:14]=[CH:13][N:18]=[C:17]([NH:2][C@@H:3]2[CH2:7][C@H:6]([CH2:8][OH:9])[C@@H:5]([OH:10])[C@H:4]2[OH:11])[CH:16]=1
null
CC(C)O
CCN(CC)CC
null
90
143.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,406,579
[H-]
[Na+]
null
null
ord_dataset-7456bda2326f4bebaa874a5474d4cc0d
2014-01-01T00:03:00
true
Preparation according to Preparation 14. 3-(3-Chloro-2-fluorophenyl)-3-methoxypyrrolidine (3.44 g, 15 mmol), dry dimethyl formamide (5 mL), sodium hydride (60% dispersion in mineral oil, 0.720 g, 18 mmol). Benzylbromide (1.78 mL, 15 mmol) in dry dimethyl formamide (5 mL). Work up according to Preparation 14. Purification by flash column chromatography on silica gel (ethyl acetate) gave the title compound (3.83 g, 80%). MS m/z (rel. intensity, 70 eV) 304 (14), 289 (16), 133 (65), 132 (35), 91 (bp).
COC1(c2cccc(Cl)c2F)CCN(Cc2ccccc2)C1
null
BrCc1ccccc1
COC1(c2cccc(Cl)c2F)CCNC1
null
[Cl:1][C:2]1[C:3]([F:15])=[C:4]([C:8]2([O:13][CH3:14])[CH2:12][CH2:11][NH:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[CH2:18]([N:10]1[CH2:11][CH2:12][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:15])([O:13][CH3:14])[CH2:9]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
null
CN(C)C=O
null
null
null
null
79.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,090,050
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-52a37d876ddb453e86de0c15fa233d29
2011-01-01T00:09:00
true
To 3-(3-(1,2,4-oxadiazol-3-yl)phenethoxy)-N-cyclohexyl-N-(2,2-dimethoxyethyl)propanamide [Example 11, Step ii)] (500 mg) in NMP (4 mL) was added p-toluenesulfonic acid (441 mg) and the mixture stirred for 8 h. After work-up the material was used in the next step directly.
O=CCN(C(=O)CCOCCc1cccc(-c2ncon2)c1)C1CCCCC1
null
COC(CN(C(=O)CCOCCc1cccc(-c2ncon2)c1)C1CCCCC1)OC
null
null
[O:1]1[CH:5]=[N:4][C:3]([C:6]2[CH:7]=[C:8]([CH:29]=[CH:30][CH:31]=2)[CH2:9][CH2:10][O:11][CH2:12][CH2:13][C:14]([N:16]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:17][CH:18](OC)[O:19]C)=[O:15])=[N:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN1C(=O)CCC1>[O:1]1[CH:5]=[N:4][C:3]([C:6]2[CH:7]=[C:8]([CH:29]=[CH:30][CH:31]=2)[CH2:9][CH2:10][O:11][CH2:12][CH2:13][C:14]([N:16]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH2:17][CH:18]=[O:19])=[O:15])=[N:2]1
8
CN1CCCC1=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,658,249
[Pd+2]
[OH-]
null
null
ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0
2015-01-01T00:11:00
true
A mixture of 6-benzyl-2-(4-((2,4-difluorophenyl)fluoromethyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (60 mg, 0.096 mmol) and Pd(OH)2 on carbon, (20 wt %, 6 mg, 8.54 μmol) in THF (960 μL) was stirred under an atmosphere of hydrogen gas (balloon) at rt. After 2 h, the mixture was purified by HPLC Method A to give the title compound as a TFA salt (47.6 mg, 93%) as a yellow foam. 1H NMR (400 MHz, methanol-d4) δ ppm 1.23 (dd, J=6.4, 2.4 Hz, 6H), 1.41-1.49 (m, 1H), 1.52-1.74 (m, 2H), 1.98-2.14 (m, 2H), 2.68 (qd, J=12.6, 2.5 Hz, 2H), 2.96 (t, J=6.3 Hz, 2H), 3.40-3.51 (m, 2H), 3.52 (t, J=6.3 Hz, 2H), 4.10-4.16 (m, 1H), 4.16 (s, 2H), 5.53 (dd, J=46.5, 7.6 Hz, 1H), 6.97-7.08 (m, 2H), 7.47-7.55 (m, 1H); ESI-MS m/z [M+H]+ 420.3.
CC(C)Nc1nc2c(nc1N1CCC(C(F)c3ccc(F)cc3F)CC1)CCNC2
null
CC(C)Nc1nc2c(nc1N1CCC(C(F)c3ccc(F)cc3F)CC1)CCN(Cc1ccccc1)C2
null
null
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].C([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[N:18][C:19]([NH:41][CH:42]([CH3:44])[CH3:43])=[C:20]([N:25]3[CH2:30][CH2:29][CH:28]([CH:31]([C:33]4[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=4[F:40])[F:32])[CH2:27][CH2:26]3)[N:21]=2)[CH2:16]1)C1C=CC=CC=1>C1COCC1.[OH-].[OH-].[Pd+2]>[F:40][C:34]1[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=1[CH:31]([F:32])[CH:28]1[CH2:29][CH2:30][N:25]([C:20]2[N:21]=[C:22]3[CH2:23][CH2:24][NH:15][CH2:16][C:17]3=[N:18][C:19]=2[NH:41][CH:42]([CH3:44])[CH3:43])[CH2:26][CH2:27]1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]
2
O=C(O)C(F)(F)F
C1CCOC1
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
149,493
null
null
null
null
ord_dataset-f222e615b1f74f0fabef9cd9b98516b7
1986-01-01T00:10:00
true
3-Hydroxytetrahydrofuran (0.04 mole), toluene (50 ml) and triethylamine (0.04 mole) are charged into a glass reaction vessel equipped with a mechanical stirrer and addition funnel. A solution of 2-chloro-5-(2-bromo-4-trifluoromethylphenoxy)benzoyl chloride (0.04 mole) in toluene (20 ml) is slowly added at room temperature with stirring. After the addition is completed, stirring is continued for a period of about eight hours. After this time, the reaction mixture is washed with water and dried over anhydrous magnesium sulfate. The dried solution is then stripped of solvent under reduced pressure leaving a residue. This residue is purified by silica gel chromatography using toluene and ethyl acetate/toluene mixture as the eluant to yield the desired product 3-tetrahydrofuryl 2-chloro-5-(2-bromo-4-trifluoromethylphenoxy)benzoate.
O=C(OC1CCOC1)c1cc(Oc2ccc(C(F)(F)F)cc2Br)ccc1Cl
null
O=C(Cl)c1cc(Oc2ccc(C(F)(F)F)cc2Br)ccc1Cl
OC1CCOC1
null
[OH:1][CH:2]1[CH2:6][CH2:5][O:4][CH2:3]1.C(N(CC)CC)C.[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:26]=2[Br:35])=[CH:20][C:16]=1[C:17](Cl)=[O:18]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:27][C:26]=2[Br:35])=[CH:20][C:16]=1[C:17]([O:1][CH:2]1[CH2:6][CH2:5][O:4][CH2:3]1)=[O:18]
8
CCN(CC)CC
Cc1ccccc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,026,957
O=C(Cl)C(=O)Cl
null
null
null
ord_dataset-83acb82dc5ba4f7aba439b9875aaac43
2011-01-01T00:02:00
true
To a solution of oxalyl chloride (27 g, 214 mmol) in anhydrous DCM (300 ml) at −78° C. under nitrogen was added anhydrous DMSO (33.4 g, 428 mmol) and the mixture was stirred at −78° C. for 20 min. A solution of 2,2-dimethylhept-4-yn-1-ol (20 g, 142 mmol) in anydrous DCM (50 ml) was added slowly over a period of 25 min. The reaction mixture was stirred at −78° C. for 2 hours and quenched by the addition of TEA (165 ml, 1.14 mol) and diluted with water (700 ml). The organic layer was separated and washed with a 1.5M aqueous solution of HCl (200 ml), water and brine. The organic layer was dried (MgSO4) and the solvent was removed under reduced pressure to afford the titled compound as a pale brown liquid (16.5 g, 87%). TLC: Pet. ether/EtOAc (8/2): Rf=0.75.
CCC#CCC(C)(C)C=O
null
CCC#CCC(C)(C)CO
null
null
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]([CH3:20])([CH2:15][C:16]#[C:17][CH2:18][CH3:19])[CH2:13][OH:14]>C(Cl)Cl.O>[CH3:11][C:12]([CH3:20])([CH2:15][C:16]#[C:17][CH2:18][CH3:19])[CH:13]=[O:14]
0.33
O
ClCCl
CS(C)=O
-78
84.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,038,496
[Na+]
[OH-]
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
The title compound was synthesized from ethyl 6-(biphenyl-4-ylmethyl)-1,4-dihydrocyclopenta[b]pyrrole-2-carboxylate (0.0343 g, 0.1 mmol, 1 equiv) and sodium hydroxide (0.36 mL, 3.6 mmol, 10 M, 35 equiv), according to General Procedure 7. The resulting product was purified by preparative HPLC using the Chromeleon purification system. A 0.1% formic acid/1% acetonitrile mixture in water (aqueous phase) and methanol (no modifier added—organic phase) using a 50 mm Dynamax HPLC C-18 column at 28 mL/min (initial gradient of 70% methanol and increasing to 100% over 7 minutes) afforded the title compound (15.7 mg, 50%) with purity by HPLC of 93.3% (UV). LCMS m/e 316.2 (M−H). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.08-2.20 (m, 1H) 2.41-2.50 (m, 2H) 2.75 (dd, J=13.62, 8.54 Hz, 1H) 3.06-3.12 (m, 1H) 6.55 (s, 1H) 7.24 (d, J=8.10 Hz, 2H) 7.28-7.33 (m, 1H) 7.41 (t, J=7.61 Hz, 2H) 7.53 (d, J=8.13 Hz, 2H) 7.60 (d, J=7.20 Hz, 2H) 8.50 (s, 1H).
O=C(O)c1cc2c([nH]1)C(Cc1ccc(-c3ccccc3)cc1)CC2
null
CCOC(=O)c1cc2c([nH]1)C(Cc1ccc(-c3ccccc3)cc1)=CC2
null
null
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8]2[C:12]3[NH:13][C:14]([C:16]([O:18]CC)=[O:17])=[CH:15][C:11]=3[CH2:10][CH:9]=2)=[CH:3][CH:2]=1.[OH-].[Na+]>>[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:2]=[CH:3][C:4]([CH2:7][CH:8]2[C:12]3[NH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9]2)=[CH:5][CH:6]=1
null
null
null
null
null
null
49.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,081,001
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-afd812677c134591a99f46ce28de2524
2011-01-01T00:08:00
true
To a solution of 4′-{[2-ethyl-1-(4-hydroxyphenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.4 g) in N,N-dimethylacetamide (10 mL) were added 1-iodo-2,2-dimethylpropane (0.26 g) and cesium carbonate (0.44 g), and the mixture was stirred at 120° C. for 24 hr. The mixture was allowed to cool to room temperature and the insoluble material was filtered off. The filtrate was diluted with ethyl acetate, washed with 1 M hydrochloric acid, saturated sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound as a pale-yellow solid (0.40 g, 87%).
CCCc1nc(CC)n(-c2ccc(OCC(C)(C)C)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
null
CC(C)(C)CI
CCCc1nc(CC)n(-c2ccc(O)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
null
[CH2:1]([C:3]1[N:4]([C:28]2[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=2)[C:5](=[O:27])[C:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=1)[CH3:2].I[CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[CH3:36][C:37]([CH3:40])([CH3:39])[CH2:38][O:34][C:31]1[CH:32]=[CH:33][C:28]([N:4]2[C:5](=[O:27])[C:6]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:15][CH:14]=3)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=[C:3]2[CH2:1][CH3:2])=[CH:29][CH:30]=1
24
CC(=O)N(C)C
null
null
120
86.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,573,686
[BH4-]
[Na+]
null
null
ord_dataset-9741bb5fd93044078df2a45f45733054
2015-01-01T00:04:00
true
To a solution of the product from Example 1A (1.0 g, 3.05 mmol) in anhydrous THF (30 ml) at 0° C. was added sodium borohydride (0.357 g, 9.44 mmol). The resulting mixture was stirred at 50° C. overnight. The cooled mixture was poured into water, extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated in vacuo. The resulting solid was triturated with dichloromethane to give a tan solid that was collected by filtration and dried to give the title compound (0.82 gm, 81% yield).
O=[N+]([O-])c1ccc(C(O)CCC(O)c2ccc([N+](=O)[O-])cc2)cc1
null
O=C(CCC(=O)c1ccc([N+](=O)[O-])cc1)c1ccc([N+](=O)[O-])cc1
null
null
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:24])[CH2:11][CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].[BH4-].[Na+].O>C1COCC1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([OH:24])[CH2:11][CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[OH:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]
8
O
C1CCOC1
null
50
null
80.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
949,704
N
[OH-]
[Zn]
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
To a solution of 2-morpholin-4-yl-8-(1-nitro-dibenzofuran-4-yl)-1-benzopyran-4-one (32, 2.5 mmol, 1.11 g) in acetic acid (50 ml) was added zinc dust (25 mmol, 1.64 g), portionwise over ten minutes. The mixture was then stirred at room temperature for 2 hrs, whereupon it was filtered through a Celite™ pad which was washed with methanol (20 ml) and CH2Cl2 (20 ml). Solvents were removed in vacuo to give a slurry which was then diluted with ammonia hydroxide (30 ml) and the resulting solid removed by filtration. The residue was purified by flash chromatography (SiO2) using MeOH; CH2Cl2-1:99 as eluent to give the desired product (75%) in analytically pure form. m/z 413.5 [M+H]+ (Rt=4.27 min).
Nc1ccc(-c2cccc3c(=O)cc(N4CCOCC4)oc23)c2oc3ccccc3c12
null
O=c1cc(N2CCOCC2)oc2c(-c3ccc([N+](=O)[O-])c4c3oc3ccccc34)cccc12
null
null
[N:1]1([C:7]2[O:8][C:9]3[C:17]([C:18]4[C:23]5[O:24][C:25]6[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=6[C:22]=5[C:21]([N+:31]([O-])=O)=[CH:20][CH:19]=4)=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1>C(O)(=O)C.[OH-].N.[Zn]>[NH2:31][C:21]1[C:22]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[O:24][C:23]=2[C:18]([C:17]2[C:9]3[O:8][C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:12][C:11](=[O:13])[C:10]=3[CH:14]=[CH:15][CH:16]=2)=[CH:19][CH:20]=1
2
CC(=O)O
null
null
25
75
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
867,882
null
null
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
A mixture of compound 59 (41 mg, 0.15 mmol), triethylamine (83 uL, 0.60 mmol), α-ethyl-benzyl isocyanate (29 mg, 0.18 mmol) in methylene chloride (1.2 mL) was stirred overnight. TLC analysis indicated the completion the reaction. Removal of solvents gave the crude material, which was purified by preparative TLC plate (15% EtOAc in hexanes), yielding 38.2 mg of compound 60 (59%): LC-MS purity: 98.1%; 1HNMR (300 MHz, CDCl3): 0.95 (t, 3H), 1.92 (m, 2H), 2.69 (m, 2H), 3.30 (m, 1H), 3.83 (s, 3H), 4.22 (d, 1H), 4.85 (q, 1H), 5.18 (m, 4H), 5.80 (m, 1H), 6.85 (br, d, 1H), 7.45 (m, 9H). Anal. C25H28N2O5, Mol. Wt.: 436.5. Found: ESI-MS: 437.1 (M+H)+.
C=CC[C@H]1C(=O)N(C(=O)NC(CC)c2ccccc2)[C@@H]1C(=O)OCc1ccc(OC)cc1
null
C=CC[C@H]1C(=O)N[C@@H]1C(=O)OCc1ccc(OC)cc1
CCC(N=C=O)c1ccccc1
null
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][O:8][C:9]([C@@H:11]2[C@@H:14]([CH2:15][CH:16]=[CH2:17])[C:13](=[O:18])[NH:12]2)=[O:10])=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH2:28]([CH:30]([N:37]=[C:38]=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:29]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]([C@@H:11]2[C@@H:14]([CH2:15][CH:16]=[CH2:17])[C:13](=[O:18])[N:12]2[C:38](=[O:39])[NH:37][CH:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:28][CH3:29])=[O:10])=[CH:19][CH:20]=1
8
CCN(CC)CC
ClCCl
null
null
null
58.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,546,236
null
null
null
null
ord_dataset-cac8df8aff894288876df4e093c9877f
2015-01-01T00:02:00
true
A stirred mixture of 3-iodo-1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)pyrazin-2(1H)-one (750 mg, 1.81 mmol), ammonia (7 M solution in MeOH, 2 mL, 14 mmol), and DMSO (1.5 mL), was heated in a Biotage Microwave Synthesizer at 150° C. for 15 min. The mixture was cooled to and partitioned between EtOAc and a 1:1 mixture of water and brine. The organic layer was separated, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 100% DCM to 2% MeOH in DCM to afford 3-amino-1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)pyrazin-2(1H)-one (149 mg) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 7.96 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.43 (dd, J=1.5, 8.4 Hz, 1H), 6.92 (d, J=4.7 Hz, 1H), 6.65-6.67 (br m, 3H), 5.11 (s, 2H), 2.78 (s, 3H); LCMS (ESI) m/z 305 (M+H)+.
CSc1nc2ccc(Cn3ccnc(N)c3=O)cc2s1
null
CSc1nc2ccc(Cn3ccnc(I)c3=O)cc2s1
N
null
I[C:2]1[C:3](=[O:20])[N:4]([CH2:8][C:9]2[CH:19]=[CH:18][C:12]3[N:13]=[C:14]([S:16][CH3:17])[S:15][C:11]=3[CH:10]=2)[CH:5]=[CH:6][N:7]=1.[NH3:21]>CS(C)=O>[NH2:21][C:2]1[C:3](=[O:20])[N:4]([CH2:8][C:9]2[CH:19]=[CH:18][C:12]3[N:13]=[C:14]([S:16][CH3:17])[S:15][C:11]=3[CH:10]=2)[CH:5]=[CH:6][N:7]=1
null
CS(C)=O
null
null
150
27
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
951,456
[H-]
[Na+]
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
To a mixture of 1-piperidinemethanol (1.3 g, 10 mmol) and tetrahydrofuran (30 ml) was added sodium hydride (60%, 418 mg, 10 mmol) at 0° C. (external temperature), followed by stirring at room temperature for 30 minutes. Then, to the reaction mixture was added dropwise a mixture of tributyl-iodomethyl-tin (3.0 g, 7.0 mmol), tetrahydrofuran (5 ml), and N,N-dimethylformamide (30 ml) at 0° C. Then, the reaction mixture was stirred at room temperature for 1 hour. To the reaction mixture were added water and ethyl acetate, and the organic layer was separated. The organic layer was sequentially washed with water and an aqueous saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=20:1, NH silica gel) to obtain the title compound (2.1 g, 4.9 mmol, 70%).
CCCC[Sn](CCCC)(CCCC)COCCN1CCCCC1
null
CCCC[Sn](CI)(CCCC)CCCC
OCN1CCCCC1
C1CCOC1
[N:1]1([CH2:7]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[O:9]1CCC[CH2:10]1.[H-].[Na+].[CH2:16]([Sn:20]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:21]I)[CH2:17][CH2:18][CH3:19]>C(OCC)(=O)C.O.CN(C)C=O>[CH2:16]([Sn:20]([CH2:21][O:9][CH2:10][CH2:7][N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH2:25][CH3:26])[CH2:17][CH2:18][CH3:19]
0.5
CCOC(C)=O
CN(C)C=O
O
25
70
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
292,119
[Na+]
[OH-]
null
null
ord_dataset-6c3ec086c8c9475e8d31a44641b49e02
1994-01-01T00:06:00
true
Aqueous sodium hydroxide (15.4 g, 192 mL, 0.08 g/mL solution, 0.38 mol) was added to a solution of dipeptide 25 (187.1 g, ca. 0.38 mol), water (360 mL) and MeOH (ca. 6 L). The solution was stirred at room temperature until hydrolysis was complete (ca. 24 hours). The disappearance of the starting peptide was established by HPLC analysis. The solution was concentrated in vacuo to a residue which was dissolved in water (ca. 1 L). The aqueous layer (pH ca. 10) was then extracted with EtOAc (2×500 mL) in a separatory funnel. The resulting aqueous phase was adjusted to a pH of 5 with concentrated HCl at which point a crystalline precipitate formed. The solid was collected by vacuum filtration and dried in vacuo (148.4 g, 0.31 mol, 82%). The pH of the filtrate was adjusted to 4.5. A second crop of solid was again collected by vacuum filtration and dried in vacuo (20.2 g, 0.043 mol, 11%). 1H NMR showed both samples to contain dipeptide 26 in high purity. In two repetitions of this reaction, yields of 83% (ca. 0.06 mole scale) and 58% (ca. 0.3 mole scale) were obtained.
O=C(N[C@@H](Cc1c[nH]cn1)C(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)O)OCc1ccccc1
null
COC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)OCc1ccccc1
null
null
[OH-].[Na+].C[O:4][C:5](=[O:38])[C@@H:6]([CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][CH:30]=1)[NH:7][C:8](=[O:27])[C@H:9]([CH2:21][C:22]1[N:26]=[CH:25][NH:24][CH:23]=1)[NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].O>CO>[CH2:14]([O:13][C:11]([NH:10][C@H:9]([C:8]([NH:7][C@@H:6]([C:5]([OH:38])=[O:4])[CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][CH:30]=1)=[O:27])[CH2:21][C:22]1[N:26]=[CH:25][NH:24][CH:23]=1)=[O:12])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
null
CO
O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,645,904
Cl
null
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
Title compound was prepared according to the method employed to prepare (S)-1-((S)-8-(5-(4-(6-(2-((S)-1-((R)-2-(methoxycarbonylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamic acid methyl ester, except that methyl (S)-2-((S)-8-(6-(9,9-difluoro-7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethylcarbamate 3× HCl salt was used instead of methyl (S)-3-methyl-1-oxo-1-((S)-8-(5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)butan-2-ylcarbamate 3HCl salt. MS (ESI) m/z 972.54 [M+H]+. (30 mg, 43%).
COC(=O)N[C@H](C(=O)N1CC2(C[C@H]1c1nc3ccc(-c4ccc5c(c4)C(F)(F)c4cc(-c6cnc([C@@H]7CCCN7C(=O)[C@H](NC(=O)OC)c7ccccc7)[nH]6)ccc4-5)cc3[nH]1)OCCO2)C1CCOCC1
null
COC(=O)N[C@H](C(=O)N1CC2(C[C@H]1c1ncc(-c3ccc(-c4ccc5cc(-c6cnc([C@@H]7CCCN7C(=O)[C@H](NC(=O)OC)c7ccccc7)[nH]6)ccc5c4)cc3)[nH]1)OCCO2)C(C)C
COC(=O)N[C@H](C(=O)N1CC2(C[C@H]1c1nc3ccc(-c4ccc5c(c4)C(F)(F)c4cc(-c6cnc([C@@H]7CCCN7)[nH]6)ccc4-5)cc3[nH]1)OCCO2)C1CCOCC1
null
COC(=O)N[C@@H](C(C)C)C(N1[C@H](C2NC(C3C=CC(C4C=CC5C(=CC=C(C6NC([C@@H]7CCCN7[C:48](=[O:61])[C@H:49]([NH:56][C:57]([O:59][CH3:60])=[O:58])[C:50]7[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=7)=NC=6)C=5)C=4)=CC=3)=CN=2)CC2(OCCO2)C1)=O.[F:66][C:67]1([F:122])[C:79]2[CH:78]=[C:77]([C:80]3[CH:81]=[CH:82][C:83]4[N:87]=[C:86]([C@@H:88]5[CH2:96][C:91]6([O:95][CH2:94][CH2:93][O:92]6)[CH2:90][N:89]5[C:97](=[O:110])[C@@H:98]([NH:105][C:106](=[O:109])[O:107][CH3:108])[CH:99]5[CH2:104][CH2:103][O:102][CH2:101][CH2:100]5)[NH:85][C:84]=4[CH:111]=3)[CH:76]=[CH:75][C:74]=2[C:73]2[C:68]1=[CH:69][C:70]([C:112]1[NH:116][C:115]([C@@H:117]3[CH2:121][CH2:120][CH2:119][NH:118]3)=[N:114][CH:113]=1)=[CH:71][CH:72]=2.Cl>>[CH3:108][O:107][C:106](=[O:109])[NH:105][C@@H:98]([CH:99]1[CH2:104][CH2:103][O:102][CH2:101][CH2:100]1)[C:97]([N:89]1[C@H:88]([C:86]2[NH:85][C:84]3[CH:111]=[C:80]([C:77]4[CH:76]=[CH:75][C:74]5[C:73]6[C:68](=[CH:69][C:70]([C:112]7[NH:116][C:115]([C@@H:117]8[CH2:121][CH2:120][CH2:119][N:118]8[C:48](=[O:61])[C@H:49]([NH:56][C:57]([O:59][CH3:60])=[O:58])[C:50]8[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=8)=[N:114][CH:113]=7)=[CH:71][CH:72]=6)[C:67]([F:66])([F:122])[C:79]=5[CH:78]=4)[CH:81]=[CH:82][C:83]=3[N:87]=2)[CH2:96][C:91]2([O:95][CH2:94][CH2:93][O:92]2)[CH2:90]1)=[O:110]
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