Trifluoroacetic acid → N-(1-(1-acryloyl-1,4-diazepan-6-yl)-7-chloro-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide

HRID 60076Notes

Reaction equation

HRID 60076 reaction equation
[C:1]([N:5]1[CH2:11][CH:10]([N:12]2[C:16]3[C:17]([Cl:21])=[CH:18][CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[NH:22][C:23](=[O:31])[C:24]2[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=2)[CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1)(=[O:4])[CH:2]=[CH2:3].FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]([N:5]1[CH2:11][CH:10]([N:12]2[C:16]3[C:17]([Cl:21])=[CH:18][CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[NH:22][C:23](=[O:31])[C:24]2[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=2)[CH2:9][NH:8][CH2:7][CH2:6]1)(=[O:4])[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 72704395tert-butyl 4-acryloyl-6-(7-chloro-2-(2-methylisonicotinamido)-1H-benzo[d]imidazol-1-yl)-1,4-diazepane-1-carboxylate

Product 1

HCID 72704396N-(1-(1-acryloyl-1,4-diazepan-6-yl)-7-chloro-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of Example 12 (150 mg, 0.278 mmol) in CH2Cl2 (2 mL) was treated with a 1:1 solution of 2,2,2-trifluoroacetic acid in CH2Cl2 (4 mL) and stirred for 90 min. The volatiles were removed under reduced pressure, the residue partitioned between CH2Cl2 and saturated aqueous Na2CO3, the layers separated, and the aqueous phase extracted with CH2Cl2 (2×). The combined organics were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to afford the title compound (Example 13). 1H NMR (400 MHz, MeOD) δ 8.58 (d, J=5.2 Hz, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.88 (s, 1H), 7.60-7.47 (m, 1H), 7.31 (s, 1H), 7.30-7.21 (m, 1H), 6.83 (dd, J=10.6, 16.8 Hz, 1H), 6.31 (d, J=16.7 Hz, 1H), 6.17-5.85 (m, 1H), 5.78 (dd, J=10.5, 34.2 Hz, 1H), 4.79-4.39 (m, 1H), 4.37-4.12 (m, 1H), 4.12-3.56 (m, 1H), 3.55-3.34 (m, 1H), 3.25-2.97 (m, 3H), 2.96-2.82 (m, 1H), 2.65 (s, 3H); MS calculated for C22H24ClN6O2 (M+H+) 439.16. found 439.2.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue partitioned between CH2Cl2 and saturated aqueous Na2CO3
  3. customthe layers separated
  4. extractionthe aqueous phase extracted with CH2Cl2 (2×)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b0ab7075ebbb4edd9dd79dfa768af70b
Source dataset
uspto-grants-2016_09
Patent number
US09440957B2

Reaction notes

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