N-methoxy-N-methyloxane-4-carboxamide → HCID 86640819, compound

HRID 2070909Notes

Reaction equation

HRID 2070909 reaction equation
[NH2:1][C:2]1[N:18]=[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=O)[N:4]2[N:3]=1.Br[C:20]1[N:25]2N=[C:27](N)[N:28]=[C:24]2[CH:23]=[CH:22][CH:21]=1.C([Li])C[CH2:32][CH3:33].[CH3:35][O:36]N(C)C(C1CCOCC1)=O>O1CCCC1>[CH3:35][O:36][CH2:23][C:24]1[NH:28][C:27]2[CH:32]=[C:33]([C:8]3[CH:7]=[CH:6][C:5]4[N:4]([N:3]=[C:2]([NH2:1])[N:18]=4)[C:9]=3[CH2:10][CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH:22]=[CH:21][C:20]=2[N:25]=1

Participants

6

Reactant 4

HCID 23144693N-methoxy-N-methyloxane-4-carboxamideHCID 252159395-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amineHCID 68588725HCID 68588725, compoundHCID 178418339Butyllithium

Product 1

HCID 86640819HCID 86640819, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)(tetrahydro-2H-pyran-4-yl)methanone. 5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine (11.07 g, 52.0 mmol) was suspended in anhydrous tetrahydrofuran (200 mL) and cooled to −78° C. n-Butyllithium (71.4 mL, 114 mmol) was added over 30 min and the solution was allowed to stir for 2 h (brown suspension) at −78° C. N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (9 g, 52.0 mmol) dissolved in tetrahydrofuran (50 mL, dried over molecular sieves) was added dropwise via syringe. The reaction was stirred for 1 h at −78° C. and allowed slowly warm to room temperature for 3 h (reaction became clear solution as it warmed up to room temperature.). LCMS analysis showed the desired product. The reaction was quenched with saturated sodium bicarbonate solution. The layers were separated and the aqueous was extracted with ethyl acetate (2×200 mL). The organics were dried with sodium sulfate, and the volatiles removed in vacuo. The crude was purified by crystallization from ethyl acetate to give (2-amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)(tetrahydro-2H-pyran-4-yl)methanone (8.4 g, 34.1 mmol, 65.6% yield) as a yellow solid. MS (ESI) m/z 247.0 [M+1]+.

Workup

  1. additionwas added over 30 min
  2. additionwas added dropwise via syringe
  3. stirringThe reaction was stirred for 1 h at −78° C.
  4. temperatureallowed slowly warm to room temperature for 3 h (
  5. customreaction
  6. temperaturewarmed up to room temperature

Sources & evidence

ORD record
ord-a57e791060d44ff086a48426feb3857c
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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