Triethylamine → 2-fluoroethyl 4-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylate

HRID 1622899Notes

Reaction equation

HRID 1622899 reaction equation
Cl.[CH3:2][N:3]1[C:7]2=[N:8][C:9]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:10][CH:11]=[C:6]2[C:5]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][C:21]2=[O:26])=[CH:4]1.C(N(CC)CC)C.[C:34](Cl)(=[O:39])[O:35][CH2:36][CH2:37][F:38]>C(Cl)Cl>[CH3:2][N:3]1[C:7]2=[N:8][C:9]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:10][CH:11]=[C:6]2[C:5]([N:20]2[CH2:25][CH2:24][N:23]([C:34]([O:35][CH2:36][CH2:37][F:38])=[O:39])[CH2:22][C:21]2=[O:26])=[CH:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10017Carbonochloridic acid, 2-fluoroethyl esterHCID 1317316621-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]piperazin-2-one, hydrochloride

Product 1

HCID 866945682-fluoroethyl 4-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]-3-oxopiperazine-1-carboxylateYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]piperazin-2-one, hydrochloride (0.15 g, 0.40 mmol) and triethylamine (0.121 g, 1.20 mmol) in DCM (15 mL) is added dropwise 2-fluoroethyl carbonochloridate (0.076 g, 0.602 mmol) at room temperature, and the reaction mixture is stirred for 3 h. The reaction is quenched with a saturated solution of sodium bicarbonate (20 mL) at 0° C. and extracted with DCM (3×50 mL). The combined organic layers are dried over sodium sulphate, filtered and concentrated in vacuo. The residue is purified on neutral alumina, eluting with 1% MeOH in DCM to give a product, which on triturating in Et2O, affords the title compound (0.07 g, 0.164 mmol) as an off-white solid. MS (m/z): 428 (M+1). 1H-NMR (400 MHz, DMSO-d6): δ 3.68 (s, 3H), 3.77 (m, 4H), 4.17 (bs, 2H), 4.28 (t, 1H), 4.35 (t, 1H), 4.58 (t, 1H), 4.71 (t, 1H), 5.49 (s, 2H), 6.66 (d, 1H), 7.30-7.34 (m, 2H), 7.50 (d, 1H), 7.77-7.83 (m, 2H), 8.56 (d, 1H).

Workup

  1. customThe reaction is quenched with a saturated solution of sodium bicarbonate (20 mL) at 0° C.
  2. extractionextracted with DCM (3×50 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified on neutral alumina
  7. washeluting with 1% MeOH in DCM
  8. customto give a product, which
  9. customon triturating in Et2O

Sources & evidence

ORD record
ord-a6256234b78a4915b80e3bcdcdbc445e
Source dataset
uspto-grants-2014_07
Patent number
US08778946B2

Reaction notes

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