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 1362072Notes

Reaction equation

HRID 1362072 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-326188041bea4bb0a6080ea370941e16
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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