Alternatived Products of [ 1038866-44-2 ]
Alternatived Products of [ 1038866-44-2 ]
Product Details of [ 1038866-44-2 ]
CAS No. : | 1038866-44-2 | MDL No. : | MFCD21608029 |
Formula : |
C11H14ClN3O2
|
Boiling Point : |
834.9°C at 760 mmHg |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 255.70 | Pubchem ID : | 66687106 |
Synonyms : |
|
Computed Properties of [ 1038866-44-2 ]
TPSA :Topological Polar Surface Area |
63.2 |
H-Bond Acceptor Count : |
4 |
XLogP3 : |
- |
H-Bond Donor Count : |
3 |
SP3 : |
0.45 |
Rotatable Bond Count : |
0 |
Safety of [ 1038866-44-2 ]
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H317-H319 | Packing Group: | N/A |
GHS Pictogram: |
|
Application In Synthesis of [ 1038866-44-2 ]
- Upstream synthesis route of [ 1038866-44-2 ]
- Downstream synthetic route of [ 1038866-44-2 ]
- 1
[ 883984-95-0 ]

[ 1038866-44-2 ]
Yield | Reaction Conditions | Operation in experiment |
50% |
With hydrogen In ethanol at 20℃; for 9.00 h; |
Step 3: spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride 16.4 g (42.4 mmol) benzyl 7'-chloro-2'-oxo-1'.2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d][1,3]oxazine]-1-carboxylate and 2.00 g palladium(Pd/C 10percent) in 500 mL EtOH were hydrogenated in a hydrogen atmosphere for 6 h at RT. Then another 1.0 g palladium (Pd/C 10percent) were added the mixture was hydrogenated for a further 3 h at RT in a hydrogen atmosphere. After filtration of the reaction mixture the solvent was eliminated in vacuo. The residue was triturated with EtOH, the precipitate formed was suction filtered, washed with EtOH and dried. Yield: 5.40 g (50percent of theoretical) ESI-MS: m/z=220 (M+H)+ Rt(HPLC): 0.90 min (method C) |
50% |
With hydrogen In ethanol at 20℃; for 9.00 h; |
Step 3: spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride 16.40 g (0.04 mol) benzyl 7'-chloro-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3d]-[1,3]oxazine]-1-carboxylate and 2.00 g palladium(Pd/C 10percent) in 500 mL EtOH were hydrogenated for 6 h at RT in a hydrogen atmosphere. Then 1 g of palladium (Pd/C 10percent) were additionally added and the mixture was hydrogenated for a further 3 h at RT in a hydrogen atmosphere. After filtration of the reaction mixture the solvent was eliminated in vacuo. The residue was triturated with EtOH, the precipitate formed was suction filtered, washed with EtOH and dried in the drying cupboard for 3 h at 50° C.Yield: 5.40 g (50percent of theoretical)ESI-MS: m/z=220 (M+H)+ Rt(HPLC): 0.90 min (method C) |
Reference:
[1] Patent: US2011/21500, 2011, A1. Location in patent: Page/Page column 46
[2] Patent: US2012/149698, 2012, A1. Location in patent: Page/Page column 26
- 1
-
[ 1038866-44-2 ]

-
[ 1185274-82-1 ]

-
[ 7693-46-1 ]

-
[ 1185274-53-6 ]
Yield | Reaction Conditions | Operation in experiment |
|
|
To a solution of (7lambda)-4-chloro-10-[l-(trifluoromethyl)cyclopropyl]-3,6,7,12- tetrahydroimidazo[r,2':l,7]azepino[3,4-e]indazol-7-amine (100 mg, 0.3 mmol)],and triethylamine (120 uL, 0.9 mmole) is added p-nitrophenyl chloroformate (60 mg, 0.3 mmmol) and stirred at 0C for 1 hr. Spiro[piperidine-4,4'-pyrido[2,3-d][l,3]oxazin]-2'(1'H)-one hydrochloride [Burgey et ah WO 2006/044504], (77 mg, 0.3mmole is then added with triethylamine (120 uL, 0.675 mmol) and the reaction mixture is stirred at ambient temperature for 16 hrs. Saturated aqueous sodium carbonate (50 mL) is added and the mixture is extracted with dichloromethane (3 * 25 mL). The organic layer is washed with saturated aqueous sodium bicarbonate (3 x), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane ? 93% dichloromethane/ methanol] gives the title compound |
- 2
-
[ 45644-21-1 ]

-
[ 1038866-44-2 ]
- 3
-
[ 1038866-44-2 ]

-
[ 1231750-45-0 ]

-
[ 1231749-28-2 ]
Yield | Reaction Conditions | Operation in experiment |
25% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 10h; |
Example 781-{1-[6-(2.7-dimethyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-spiro[piperidin-4,4'-pyrido-[2,3-d][1,3]oxazin]-2'(1'H)-one; 128 mg (0.500 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 167 mg (0.500 mmol) 6-(6-chloro-pyrimidin-4-yloxy)-2-methyl-4-trifluoromethyl-1H-benzimidazole and 0.261 mL (1.50 mmol) DIPEA in 1.5 mL DMF were stirred for 10 h at RT. The reaction mixture was purified by preparative HPLC-MS. The fractions containing product were combined and freeze-dried.Yield: 65 mg (25% of theory)ESI-MS: m/z=512 (M+H)+ Rt (HPLC): 3.0 min (method C) |
- 4
-
[ 1038866-44-2 ]

-
[ 1231750-39-2 ]

-
[ 1231749-17-9 ]
Yield | Reaction Conditions | Operation in experiment |
17% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; |
Example 671-(6-(2-methoxy-7-methyl-1H-benzo[d]imidazol-5-yloxy)pyrimidin-4-yl)spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one; 64 mg (0.25 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 57 mg (0.20 mmol) 5-(6-chloropyrimidin-4-yloxy)-2-methoxy-7-methyl)-1H-benzo[d]-imidazole and 130 muL (0.75 mmol) DIPEA in 2.0 mL DMF were stirred overnight at 60 C. The reaction mixture was purified by chromatography. The fractions containing product were combined and evaporated down i.vac. to leave the aqueous residue. This was neutralised with a 1M aqueous NaOH solution. The precipitate formed was suction filtered, washed and dried.Yield: 20 mg (17% of theory)ESI-MS: m/z=474 (M+H)+ Rt(HPLC): 1.10 min (method B) |
- 5
-
[ 1038866-44-2 ]

-
[ 1231750-29-0 ]

-
[ 1231749-12-4 ]
Yield | Reaction Conditions | Operation in experiment |
44% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃; |
Example 631-(6-(7-methyl-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yloxy)pyrimidin-4-yl)spiro-[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one; 21 mg (0.08 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 22 mg (0.07 mmol) 5-(6-chloropyrimidin-4-yloxy)-7-methyl-2-(trifluoromethyl)-1H-benzo[d]-imidazole and 40 muL (0.24 mmol) DIPEA in 2.0 mL DMF were stirred at 50 C. over the weekend. The reaction mixture was purified by chromatography. The fractions containing product were combined and evaporated down i.vac. to leave the aqueous residue. This was neutralised with a 1M aqueous NaOH solution. The precipitate formed was suction filtered, washed and dried.Yield: 18 mg (44% of theory)ESI-MS: m/z=512 (M+H)+ Rt(HPLC): 1.30 min (method B) |
- 6
-
[ 1038866-44-2 ]

-
[ 1231750-18-7 ]

-
[ 1231749-06-6 ]
Yield | Reaction Conditions | Operation in experiment |
18% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; |
Example 581-(6-(7-methyl-2-(tetrahydrofuran-3-yl)-1H-benzo[d]imidazol-5-yloxy)pyrimidin-4-yl)spiro-[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one; 138 mg (0.54 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 180 mg (0.54 mmol) 5-(6-chloropyrimidin-4-yloxy)-7-methyl-2-(tetrahydrofuran-3-yl)-1H-benzo[d]imidazole and 280 muL (1.62 mmol) DIPEA in 5.0 mL DMF were stirred overnight at 60 C. The reaction mixture was combined with ice water. The precipitate formed was suction filtered and purified by chromatography. The fractions containing product were combined and evaporated down i.vac. to leave the aqueous residue. This was neutralised with an aqueous NaHCO3 solution and extracted with ethyl acetate. The organic phase was dried and evaporated down i.vac.Yield: 50 mg (18% of theory)ESI-MS: m/z=514 (M+H)+ Rt(HPLC): 2.88 min (method L) |
- 7
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[ 1038866-44-2 ]

-
[ 1231749-69-1 ]

-
[ 1231749-21-5 ]
Yield | Reaction Conditions | Operation in experiment |
68% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 - 60℃; |
Example 714-methyl-6-(2-methyl-6-(2'-oxo-1'.2'-dihydrospiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-1-yl)pyrimidin-4-yloxy)benzo[d]oxazol-2(3H)-one; 90 mg (0.35 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 90 mg (0.31 mmol) 6-(6-chloro-2-methylpyrimidin-4-yloxy)-4-methylbenzo[d]oxazol-2(3H)-one and 200 muL (1.16 mmol) DIPEA in 1.5 mL DMF were stirred overnight at RT. Another 90 mg (0.35 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong> and 200 muL (1.16 mmol) DIPEA were added and the mixture was stirred for 8 h at 60 C. The reaction mixture was mixed with water and stirred overnight. Then DCM was added and the mixture was stirred for a further 30 min. DCM was removed and the aqueous phase was suction filtered. The precipitate was washed with EtOH and dried.Yield: 100 mg (68% of theory)ESI-MS: m/z=475 (M+H)+ Rt(HPLC): 1.04 min (method B) |
- 8
-
[ 1038866-44-2 ]

-
[ 1231750-41-6 ]

-
[ 1231749-26-0 ]
Yield | Reaction Conditions | Operation in experiment |
36% |
With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 140℃; for 1h; |
Example 754-(4-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-6-yloxy)-6-(2'-oxo-1'.2'-dihydrospiro-[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-1-yl)nicotinonitrile; 40 mg (0.16 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 40 mg (0.12 mmol) 6-chloro-4-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-yloxy)-nicotino-nitrile and 0.08 mL (0.47 mmol) DIPEA in 0.80 mL NMP were stirred for 1 h at 140 C. The reaction mixture was purified by preparative HPLC-MS. The fractions containing product were partially evaporated down i.vac. and neutralised with aqueous NaHCO3 solution. The precipitate formed was suction filtered and dried.Yield: 47 mg (36% of theory)ESI-MS: m/z=485 (M+H)+ Rt(HPLC): 1.34 min (method B) |
- 9
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[ 1038866-44-2 ]

-
[ 1231750-49-4 ]

-
[ 1231749-20-4 ]
Yield | Reaction Conditions | Operation in experiment |
35% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 50℃; |
Example 70(R)-1-(6-(4-methyl-2-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-6-yloxy)pyrimidin-4-yl)-spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one; 166 mg (0.65 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 205 mg (0.62 mmol) (R)-6-(6-chloropyrimidin-4-yloxy)-4-methyl-2-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazole and 320 muL (1.86 mmol) DIPEA in 5.0 mL DMF were stirred overnight at 50 C. The reaction mixture was purified by chromatography. The fractions containing product were combined and evaporated down i.vac. to leave the aqueous residue. This was neutralised with an aqueous NaHCO3 solution. The precipitate formed was suction filtered, washed and dried.Yield: 110 mg (35% of theory)ESI-MS: m/z=514 (M+H)+ Rt(HPLC): 0.98 min (method B) |
- 10
-
[ 1038866-44-2 ]

-
[ 1231750-48-3 ]

-
[ 1231749-18-0 ]
Yield | Reaction Conditions | Operation in experiment |
38% |
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; |
Example 681-(6-(7-methyl-1H-indazol-5-yloxy)pyrimidin-4-yl)spiro[piperidin-4,4'-pyrido[2,3-d]-[1,3]oxazin]-2'(1'H)-one; 60 mg (0.23 mmol) <strong>[1038866-44-2]spiro[piperidin-4,4'-pyrido[2,3-d][1,3]oxazin]-2'(1'H)-one hydrochloride</strong>, 60 mg (0.23 mmol) 5-(6-chloropyrimidin-4-yloxy)-7-methyl-1H-indazole and 100 muL (0.58 mmol) DIPEA in 0.8 mL DMF were stirred at RT over the weekend. The reaction mixture was purified by chromatography. The fractions containing product were combined and evaporated down i.vac. to leave the aqueous residue. This was neutralised with an aqueous saturated NaHCO3 solution. The precipitate formed was suction filtered and dried.Yield: 40 mg (38% of theory)ESI-MS: m/z=444 (M+H)+ Rt(HPLC): 3.06 min (method C) |