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

HRID 1711840Notes

Reaction equation

HRID 1711840 reaction equation
C([O:5][C:6](=[O:30])/[CH:7]=[CH:8]/[C:9]1[CH:29]=[N:28][C:12]2[NH:13][C:14](=[O:27])[CH2:15][N:16]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH2:17][C:11]=2[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:39]>>[ClH:39].[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][N:16]2[CH2:17][C:11]3[CH:10]=[C:9](/[CH:8]=[CH:7]/[C:6]([OH:30])=[O:5])[CH:29]=[N:28][C:12]=3[NH:13][C:14](=[O:27])[CH2:15]2)=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59456913HCID 59456913, compound

Product 1

HCID 66966837(E)-3-(4-(4-Methoxybenzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochlorideYield 92%

Procedure

A suspension of (E)-3-[4-(4-methoxy-benzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester (3.54 g, 8.65 mmol) in CH2Cl2 (20 mL) was treated with TFA (20 mL). After stirring at room temperature under N2 for 25 min, the clear tan solution was concentrated in vacuo. The resulting residue was treated with anhydrous HCl (40 mL of a 4.0 M solution in dioxane, 160 mmol) and sonicated for 15 min. The solid was isolated by filtration, washed with Et2O and dried under vacuum at 50° C. for 3 d to give the title compound (3.40 g, 92%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 12.38 (br s, 1H), 11.32 (s, 1H), 8.77 (s, 1H), 8.28 (s, 1H), 7.66-7.58 (m, 3H), 7.02 (d, J=8.6 Hz, 2H), 6.63 (d, J=16.1 Hz, 1H), 4.41-4.27 (m, 5H), 3.79 (s, 3H), 3.68 (s, 2H); MS (ESI) m/e 354 (M+H)+.

Workup

  1. concentrationthe clear tan solution was concentrated in vacuo
  2. additionThe resulting residue was treated with anhydrous HCl (40 mL of a 4.0 M solution in dioxane, 160 mmol) and
  3. customsonicated for 15 min
  4. customThe solid was isolated by filtration
  5. washwashed with Et2O
  6. customdried under vacuum at 50° C. for 3 d

Sources & evidence

ORD record
ord-38bffab19ee944a1a129a0c30a4f3346
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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