Dichloromethane → (E)-3-(4-Ethoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride

HRID 1362059Notes

Reaction equation

HRID 1362059 reaction equation
C([O:5][C:6](=[O:27])/[CH:7]=[CH:8]/[C:9]1[CH:26]=[N:25][C:12]2[NH:13][C:14](=[O:24])[CH2:15][N:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:17][C:11]=2[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:36]>>[ClH:36].[CH2:22]([O:21][C:19]([CH2:18][N:16]1[CH2:17][C:11]2[CH:10]=[C:9](/[CH:8]=[CH:7]/[C:6]([OH:27])=[O:5])[CH:26]=[N:25][C:12]=2[NH:13][C:14](=[O:24])[CH2:15]1)=[O:20])[CH3:23]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59456982(E)-3-(4-Ethoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid tert-butyl ester

Product 1

HCID 66966559(E)-3-(4-Ethoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochlorideYield 88%

Procedure

A solution of (E)-3-(4-ethoxycarbonylmethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid tert-butyl ester (1.14 g, 3.04 mmol) in CH2Cl2 (8 mL) was treated with TFA (8 mL). After stirring at room temperature under N2 for 45 min, the clear tan solution was concentrated in vacuo. The resulting oil was treated with anhydrous HCl in dioxane (10 mL, 4.0 M) and sonicated until the oil was converted to a fine off-white solid. The resulting mixture was diluted with Et2O (100 mL) and stirred under N2 for 20 min. The solid was isolated by filtration, washed with Et2O, and dried under vacuum at 50° C. overnight to give the title compound (1.05 g, 88%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 10.57 (s, 1H), 8.56-8.55 (m, 1H), 8.10 (s, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 4.14-4.05 (m, 3H), 3.62-3.56 (m, 6H), 1.18 (t, J=7.1 Hz, 3H); MS (ESI) m/e 320 (M+H)+.

Workup

  1. concentrationthe clear tan solution was concentrated in vacuo
  2. additionThe resulting oil was treated with anhydrous HCl in dioxane (10 mL, 4.0 M)
  3. customsonicated until the oil
  4. additionThe resulting mixture was diluted with Et2O (100 mL)
  5. stirringstirred under N2 for 20 min
  6. customThe solid was isolated by filtration
  7. washwashed with Et2O
  8. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-4cabd3f82c524c2ea8809a3f1e5a67ee
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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