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[ CAS No. 336119-88-1 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
Chemical Structure| 336119-88-1
Chemical Structure| 336119-88-1
Structure of 336119-88-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 336119-88-1 ]

CAS No. :336119-88-1 MDL No. :MFCD20482197
Formula : C19H20ClN3O Boiling Point : -
Linear Structure Formula :- InChI Key :OWYDWUOOPZRGNZ-UHFFFAOYSA-N
M.W : 341.83 Pubchem ID :22238798
Synonyms :

Calculated chemistry of [ 336119-88-1 ]

Physicochemical Properties

Num. heavy atoms : 24
Num. arom. heavy atoms : 16
Fraction Csp3 : 0.26
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 98.86
TPSA : 60.91 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.94 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.2
Log Po/w (XLOGP3) : 3.45
Log Po/w (WLOGP) : 3.43
Log Po/w (MLOGP) : 3.49
Log Po/w (SILICOS-IT) : 3.95
Consensus Log Po/w : 3.5

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.36
Solubility : 0.0148 mg/ml ; 0.0000434 mol/l
Class : Moderately soluble
Log S (Ali) : -4.41
Solubility : 0.0133 mg/ml ; 0.0000389 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -6.43
Solubility : 0.000128 mg/ml ; 0.000000375 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.28

Safety of [ 336119-88-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 336119-88-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 336119-88-1 ]

[ 336119-88-1 ] Synthesis Path-Downstream   1~42

  • 1
  • [ 336119-88-1 ]
  • [ 89711-08-0 ]
  • [ 713526-27-3 ]
YieldReaction ConditionsOperation in experiment
With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; 1.b; 8.a b) Preparation of {2- [1- (3-BENZYL-7-CHLORO-4-OXO-3, 4-dihydro- QUINAZOLIN-2-YL)-2-METHYL-PROPYLAMINO]-ETHYL}-CARBAMIC acid tert-butyl ester: Sodium TRIACETOXYBOROHYDRIDE (172 mg, 0.81 MMOL) was added to a solution containing 2- (1-AMINO-2-METHYL-PROPYL)-3-BENZYL-7-CHLORO-3H-QUINAZOLIN-4- one (185 mg, 0.54 MMOL) (prepared using the general procedure described in WO 0130768) and tert-butyl N-(2-oxoethyl) carbamate (103 mg, 0.65 MMOL) in CH2CI2 (5.4 mL). The resulting mixture was stirred at room temperature overnight. The reaction was diluted with CH2CI2 (10 mL), washed with brine, dried and concentrated under vacuum. Purification by flash chromatography on silica gel (5-10% EtOAc in hexane) gave the title compound (105 mg) as a white solid : MS (ES) m/e 485 (M + H) +. Example 8 3-BENZYL-7-CHLORO-2- [1- (6, 6-DIMETHYL-7-OXO- [1, 4] DIAZEPAN-1-YL)-2-METHYL- PROPYL]-3H-QUINAZOLIN-4-ONE a) Preparation of {2- [1- (3-BENZYL-7-CHLORO-4-OXO-3, 4-dihydro- QUINAZOLIN-2-YL)-2-METHYL-PROPYLAMINO]-ETHYL}-CARBAM IC acid TERT-BUTYL ESTER : Following the procedure of Example 1B, 2- (1-AMINO-2-METHYL-PROPYL)-3- BENZYL-7-CHLORO-3H-QUINAZOLIN-4-ONE, (2-OXO-ETHYL)-CARBAMIC acid tert-butyl ester and sodium ACETOXYBOROHYDRIDE gave the title compound as a white solid : MS (ES) m/e 485.2 (M + H) +.
  • 2
  • [ 336119-88-1 ]
  • [ 151021-56-6 ]
  • [ 902133-15-7 ]
YieldReaction ConditionsOperation in experiment
With 4 A molecular sieve; sodium tris(acetoxy)borohydride; acetic acid In dichloromethane for 1h; 3 Step 3: 3-Benzyl-2-{ l-[(3-{ [tert-butyl(diphenyl)silyl]oxy)-2-fluoropropyl)ammo]-2- methylpropyl 1 -7-chloroquinazolin-4(3H)-one ( 1 -4) To a solution of 3-[tert-butyl(diphenyl)silyl]oxy}-2-fluoroρroρanal hβ (0.222 g, 0.673 mmol) and 2-(l-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one (prepared as described in U.S. Pat. No. 6,545,004 Bl, col. 26) (0.230 g, 0.673 mmol) in DCM (4.0 mL) was added acetic acid(few drops), 4A molecular sieves (a spatula full) and sodium triacetoxyborohydride (0.428 g, 2.00 mmol).After one hour, performed an aqueous workup and chromatographed using normal phase conditions (0%->15% EtOAc:Hx) to afford the title compound as a white foam. 1H NMR (500 MHz, CDCl3): δ 0.89-0.93 (m,6H), 0.99 (s, 9H), 1.88-1.95 (m ,2H), 2.63-2.67 (m,lH), 3.49-3.57 (m, 2H), 4.20-4.40 (m, 2H), 4.89-4.96 (m, IH), 5.86-5.93 (m, IH), 7.15-7.18 (m, 3H), 7.21-7.30 (m, 3H), 7.34-7.39 (m, 4H), 7.41-7.45 (m, 3H), 7.60-7.64 (m, 4H), 8.26 (d, J= 5 Hz, IH) ppm. MS[M+H] C38H43ClFN3O2Si = 656.30.
  • 3
  • [ 89-77-0 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 2.1: 5 h / 100 °C / Inert atmosphere 3.1: toluene / 3 h / Inert atmosphere; Dean-Stark; Reflux 3.2: 5 h / Inert atmosphere; Dean-Stark; Reflux 4.1: sodium acetate; acetic acid; bromine / 4 h / 45 °C / Inert atmosphere 5.1: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 6.1: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 4
  • [ 108-12-3 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 2.1: 5 h / 100 °C / Inert atmosphere 3.1: toluene / 3 h / Inert atmosphere; Dean-Stark; Reflux 3.2: 5 h / Inert atmosphere; Dean-Stark; Reflux 4.1: sodium acetate; acetic acid; bromine / 4 h / 45 °C / Inert atmosphere 5.1: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 6.1: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 5
  • [ 887636-73-9 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: 5 h / 100 °C / Inert atmosphere 2.1: toluene / 3 h / Inert atmosphere; Dean-Stark; Reflux 2.2: 5 h / Inert atmosphere; Dean-Stark; Reflux 3.1: sodium acetate; acetic acid; bromine / 4 h / 45 °C / Inert atmosphere 4.1: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 5.1: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 6
  • [ 587881-22-9 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: toluene / 3 h / Inert atmosphere; Dean-Stark; Reflux 1.2: 5 h / Inert atmosphere; Dean-Stark; Reflux 2.1: sodium acetate; acetic acid; bromine / 4 h / 45 °C / Inert atmosphere 3.1: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 4.1: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 7
  • [ 587881-23-0 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium acetate; acetic acid; bromine / 4 h / 45 °C / Inert atmosphere 2: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 3: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 8
  • [ 587881-24-1 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 5 h / 45 °C / Inert atmosphere 2: zinc; ammonium chloride / ethyl acetate; methanol / 0.5 h / 20 - 60 °C / Inert atmosphere
  • 9
  • [ 587881-25-2 ]
  • [ 336119-88-1 ]
YieldReaction ConditionsOperation in experiment
93% With ammonium chloride; zinc In methanol; ethyl acetate at 20 - 60℃; for 0.5h; Inert atmosphere; (±)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one (10) Activated Zn(s) was prepared in accordance with previously reported methods.2 Compound 9 (2.50 g, 6.8 mmol) was dissolved in EtOAc (30 mL) then diluted with MeOH (100 mL). Ammonium chloride (1.82 g, 34.0 mmol, 5.0 equiv.) was added and the reaction was placed under N2(g) with stirring at rt. Then activated zinc powder (2.22 g, 34.0 mmol, 5.0 equiv.) was added portionwise over 5 min before heating the reaction to 60 °C for 30 min. The reaction was monitored by TLC (20% EtOAc/hexanes, UV) and was found to be complete within 10 min. with the amine product remaining at the baseline (Rf = 0.00). Then the reaction was cooled to rt, filtered through Celite to remove the Zn and excess NH4Cl with EtOAc washing (3´20 mL), then the product was extracted by the addition of EtOAc (100 mL) and sat. NaHCO3(aq.) (100 mL). The organic fraction was then washed with brine (100 mL) and dried over anhydrous Na2SO4(s) for 30 min before filtering and removing the solvent under reduced pressure to give purified racemic compound 10 as a thick, off-white/yellow oil (2.15 g, 6.3 mmol, 93%). 1H NMR (400 MHz, DMSO-d6): δH 0.59 (d, 3H, 3JHH = 6.6 Hz, magnetically inequivalent CH3), 0.86 (d, 3H, 3JHH = 6.6 Hz, magnetically inequivalent CH3), 1.95 (s, 2H, NH2, displaced with D2O shake), 2.02 (m, 1H, CHCH(CH3)2), 3.47 (d, 1H, 3JHH = 7.4 Hz, CHCH(CH3)2), 5.37 (d, 1H, 2JHH = 16.4 Hz, roofing diastereotopic PhCH2), 5.53 (d, 1H, 2JHH = 16.4 Hz, roofing diastereotopic PhCH2), 7.19 (d, 2H, 3JHH = 7.2 Hz, o-Ph), 7.27 (m, 1H, p-Ph), 7.34 (m, 2H, m-Ph), 7.56 (dd, 1H, 3JHH = 8.6 Hz and w-coupling 4JHH = 2.0 Hz, Ar: -CH-CH-C(Cl)CH-), 7.71 (d, 1H, w-coupling 4JHH = 2.0 Hz, Ar: CH-C(Cl)-CHC(N)), 8.16 (d, 1H, 3JHH = 8.6 Hz, Ar: C-CH-CH-C(Cl)). 13C{1H} (100 MHz, DMSO-d6): δC 17.6 (CH3), 20.1 (CH3), 32.2 (CHCH(CH3)2), 45.3 (PhCH2), 58.2 (CHCH(CH3)2), 118.7 (IV° C), 126.1 (Ar: CH-C(Cl)-CHC(N)), 126.3 (2´o-Ph), 126.9 (-CH-CH-C(Cl)CH-), 127.3 (p-Ph), 128.6 (Ar: -CH-CH-C(Cl)CH), 128.7 (2´m-Ph), 136.8 (IV° C), 139.2 (IV° C), 148.0 (IV° C), 161.1 (IV° C), 162.4 (IV° C). MS m/z (MeCN) 342 (100%) [M+H+]. HRMS-ESI m/z (MeCN) found 342.1367, calcd for C19H21ClN3O 342.1368 [M+H+].
  • 10
  • [ 336119-88-1 ]
  • [ 1417617-08-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 11
  • [ 336119-88-1 ]
  • [ 1417617-10-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 12
  • [ 336119-88-1 ]
  • [ 1417617-11-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 13
  • [ 336119-88-1 ]
  • [ 1417617-12-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 14
  • [ 336119-88-1 ]
  • [ 1417617-14-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 15
  • [ 336119-88-1 ]
  • (R)-ispinesib [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 16
  • [ 336119-88-1 ]
  • [ 336113-54-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 17
  • [ 336119-88-1 ]
  • [ 1417617-15-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 18
  • [ 336119-88-1 ]
  • [ 1417617-16-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 19
  • [ 336119-88-1 ]
  • [ 1417617-18-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 20
  • [ 336119-88-1 ]
  • [ 1417617-04-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 21
  • [ 336119-88-1 ]
  • [ 1417617-19-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 22
  • [ 336119-88-1 ]
  • [ 1417617-21-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 23
  • [ 336119-88-1 ]
  • [ 1417617-22-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 4: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 24
  • [ 336119-88-1 ]
  • [ 1417617-23-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: pyridine; dicyclohexyl-carbodiimide / dichloromethane / 24 h / 20 °C
  • 25
  • [ 336119-88-1 ]
  • [ 1417617-24-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: pyridine; dicyclohexyl-carbodiimide / dichloromethane / 24 h / 20 °C
  • 26
  • [ 336119-88-1 ]
  • [ 1417617-06-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 27
  • [ 336119-88-1 ]
  • [ 1417617-09-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 28
  • [ 336119-88-1 ]
  • [ 1417617-13-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 29
  • [ 336119-88-1 ]
  • [ 336115-13-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 30
  • [ 336119-88-1 ]
  • [ 1028266-22-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 31
  • [ 336119-88-1 ]
  • [ 1417617-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 32
  • [ 336119-88-1 ]
  • [ 1417617-20-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 2 h / 20 °C / Inert atmosphere
  • 33
  • [ 336119-88-1 ]
  • [ 1314917-44-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 34
  • [ 336119-88-1 ]
  • [ 587881-27-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere
  • 35
  • [ 336119-88-1 ]
  • [ 1417617-01-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere
  • 36
  • [ 336119-88-1 ]
  • [ 1417617-03-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 37
  • [ 336119-88-1 ]
  • [ 336113-57-6 ]
  • [ 336113-58-7 ]
YieldReaction ConditionsOperation in experiment
1.65 g With O,O'-dibenzoyl-L-tartaric acid In isopropyl alcohol at 20 - 85℃; for 18h; Inert atmosphere; Chiral resolution of 2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one (10) Racemate 10 was separated into the two enantiomers by use of chiral resolution. Racemate 10 (4.15 g, 12.17 mmol) was dissolved in hot propan-2-ol (30 mL). Then (R,R)-(+)-2,3-dibenzyl-D-tartaric acid (4.36 g, 12.17 mmol, 1.0 equiv.) was dissolved in hot propan-2-ol (20 mL) and added quickly with rapid stirring to the solution of racemate 10 at 85 °C. A white precipitate formed within 1 min of mixing the two solutions. The solution was allowed to cool to rt and more propan-2-ol (20 mL) was added to effect stirring which was continued overnight (18 h). The resultant white solid was isolated by filtration and washed with cold propan-2-ol (2´20 mL). The filtrate containing mostly (S)-enantiomer had a clear golden yellow colour and was retained for further work-up. The white solid was dried over an air pump then transferred to a 250 mL round bottom flask and dissolved in boiling MeOH (~80 mL) for recrystallisation. Once the solid dissolved completely in MeOH, propan-2-ol (~80 mL, 1.0 equiv. v/v) was added quickly with rapid stirring. The solution was stirred at rt for 18 h until a white precipitate formed, which was collected by filtration and washed with propan-2-ol (15 mL). The white solid was dried in air then transferred to a 250 mL separating funnel and suspended in dichloromethane (80 mL). Then the organic mixture was washed with sat. NaHCO3(aq.) (3´80 mL), then the aqueous fractions were back extracted with dichloromethane (1´100 mL) before the organic fractions were combined, washed with brine (1´100 mL), dried over Na2SO4(s) for 30 min, filtered and then the solvent was removed under reduced pressure. The isolated colourless oil was dried in vacuo overnight to give enantiomerically pure 10-(R) (1.65 g, 4.84 mmol, 80%; NB: Yield based on the theoretical maximum of 100% (R)-enantiomer = 2.075 g [50% absolute]). The filtrate containing mostly the (S)-enantiomer was processed using the same extraction as described above. Then the procedure was repeated but with the addition of (S,S)-(-)-2,3-dibenzyl-L-tartaric acid (1.0 equiv.) to obtain enantiomerically pure 10-(S) (1.29 g, 3.78 mmol, 62%). All characterisation data for compounds 10-(R) and 10-(S) were identical to those described for the racemate 10 (vide supra).
  • 38
  • [ 336119-88-1 ]
  • [ 587881-28-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 39
  • [ 336119-88-1 ]
  • [ 1417617-02-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 40
  • [ 336119-88-1 ]
  • [ 1417617-05-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 41
  • [ 336119-88-1 ]
  • [ 1417617-07-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: O,O'-dibenzoyl-L-tartaric acid / isopropyl alcohol / 18 h / 20 - 85 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 6 h / 20 °C / Inert atmosphere 3: N-ethyl-N,N-diisopropylamine / dichloromethane / 24 h / 20 °C
  • 42
  • [ 336119-88-1 ]
  • [ 58885-60-2 ]
  • [ 1314917-40-2 ]
YieldReaction ConditionsOperation in experiment
78% With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane at 20℃; for 6h; Inert atmosphere; (R)-tert-butyl (3-((1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)amino)propyl)-carbamate 13-(R) General procedure: Methods for the reductive amination of compound 10 are presented for the (R)-enantiomer. The same procedures were used for synthesis of both racemic 13 and 13-(S). Compound 10-(R) (1.54 g, 4.52 mmol) was added to a flame dried 100 mL round bottom flask and placed under Ar(g). Separately, compound 12 (0.82 g, 4.74 mmol, 1.05 equiv.) was added to a vial and dissolved in 1,2-dichloroethane (5 mL). The solution of 12 was added to the reaction vessel containing compound 10-(R) and then additional 1,2-dichloroethane (10 mL) was added with stirring at rt. Then NaBH(OAc)3 (1.34 g, 6.3 mmol, 1.4 equiv.) was added and the reaction was stirred at rt for 6 h. The reaction was monitored by TLC (40% EtOAc/hexanes/~0.1% conc. NH3, UV) with the product observed as the major spot at Rf = 0.61. The reaction was then quenched by the addition of MeOH (1 mL) and transferred to a 100 mL separating funnel. Dichloromethane (20 mL) and sat. NaHCO3(aq.) (30 mL) were added and the organic layer was collected. The aqueous layer was extracted with dichloromethane (3´30 mL), then the organic fractions were combined, washed with brine (1´30 mL), dried over Na2SO4(s) for 30 min, filtered and then the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography (20-35% EtOAc/hexane/~0.1% conc. NH3). Fractions containing product were identified by TLC, pooled,, dried over anhydrous Na2SO4(s) for 30 min, filtered and then the solvent was removed under reduced pressure. The colourless oil was then dried in vacuo overnight to give purified 13-(R) as a colourless oil that solidified over time (1.70 g, 3.4 mmol, 75%). Yield for racemate 13 = 54% and 13-(S) = 80%.
Same Skeleton Products
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