Trifluoroacetic acid → (E)-N-Methyl-N-(3-methylbenzofuran-2-ylmethyl)-3-(2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamide

HRID 1879972Notes

Reaction equation

HRID 1879972 reaction equation
C(OC([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](/[CH:19]=[CH:20]/[C:21](=[O:35])[N:22]([CH3:34])[CH2:23][C:24]3[O:25][C:26]4[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=4[C:28]=3[CH3:29])[CH:17]=[N:18][C:12]=2[NH:11][CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:34][N:22]([CH2:23][C:24]1[O:25][C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]=1[CH3:29])[C:21](=[O:35])/[CH:20]=[CH:19]/[C:16]1[CH:17]=[N:18][C:12]2[NH:11][CH2:10][CH2:9][NH:8][CH2:14][C:13]=2[CH:15]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 24891455(E)-7-{2-[Methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester

Product 1

HCID 45487682(E)-N-Methyl-N-(3-methylbenzofuran-2-ylmethyl)-3-(2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylamideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (E)-7-{2-[methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester (0.38 g, 0.80 mmol) in CH2Cl2 (4 mL) was cooled in an ice bath and then treated with TFA (4 mL). After stirring for 2 h, the mixture was concentrated under vacuum. The residue was treated with saturated NaHCO3 (25 mL) and extracted with CH2Cl2/MeOH (4×50 mL of a 98:2 mixture). The combined organic layers were dried over Na2SO4, filtered and concentrated to a light yellow solid. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 92:8) gave the title compound (0.21 g, 70%) as a white powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 8.14 (br s, 1H), 7.68-7.63 (m, 1H), 7.50-7.40 (m, 3H), 7.26-7.20 (m, 2H), 7.04-6.72 (m, 1H), 5.10 (s, 1H), 4.83-4.72 (m, 2H), 3.89 (s, 2H), 3.30-3.26 (m, 2H), 3.22-3.04 (m, 5H), 2.31 (s, 3H), 1.70 (br s, 1H); MS (ESI) m/e 377 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated under vacuum
  2. additionThe residue was treated with saturated NaHCO3 (25 mL)
  3. extractionextracted with CH2Cl2/MeOH (4×50 mL of a 98:2 mixture)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a light yellow solid
  7. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 92:8)

Sources & evidence

ORD record
ord-88d9f915ac904d62b33b538878285e77
Source dataset
uspto-grants-2012_11
Patent number
US08318720B2

Reaction notes

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