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

HRID 1362090Notes

Reaction equation

HRID 1362090 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][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]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].[N:21]1([CH2:20][CH2:19][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)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59456935HCID 59456935, compound

Product 1

HCID 66966377(E)-3-[4-(3-Morpholin-4-yl-propyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid hydrochloride

Procedure

A solution of (E)-3-[4-(3-Morpholin-4-yl-propyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester (2.21 g, 5.30 mmol) in CH2Cl2 (20 mL) was treated with TFA (20 mL). After stirring at room temperature for 30 min, the solution was concentrated in vacuo. The resulting oil was treated with anhydrous HCl (50 mL of a 4.0 M solution in dioxane, 200 mmol) and the mixture was sonicated for 1.5 h. The mixture was diluted with Et2O (200 mL) and sonicated for 15 min. The solid was isolated by filtration, washed with Et2O, and dried under vacuum at 50° C. for 5 h to give the title compound (3.08 g, quantitative) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 11.23 (br s, 2H), 8.74 (s, 1H), 8.36 (s, 1H), 7.63 (d, J=15.9, 1H), 6.63 (d, J=16.0 Hz, 1H), 4.33 (br s, 2H), 3.90 (br s, 6H), 3.24 (m, 8H), 2.22 (br s, 2H); MS (ESI) m/e 361 (M+H)+.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additionThe resulting oil was treated with anhydrous HCl (50 mL of a 4.0 M solution in dioxane, 200 mmol) and the mixture
  3. customwas sonicated for 1.5 h
  4. additionThe mixture was diluted with Et2O (200 mL)
  5. customsonicated for 15 min
  6. customThe solid was isolated by filtration
  7. washwashed with Et2O
  8. customdried under vacuum at 50° C. for 5 h

Sources & evidence

ORD record
ord-deaa52f55d344dfab9cda873933fc7ca
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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