Trifluoroacetic acid → HCID 67442777, compound

HRID 1400903Notes

Reaction equation

HRID 1400903 reaction equation
[CH:1]1([NH:4][C:5](=[O:44])[NH:6][C:7]2[CH:42]=[CH:41][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:26]=[CH:25][C:24]([CH2:27][CH2:28][N:29]([CH2:37][CH2:38][O:39][CH3:40])C(=O)OC(C)(C)C)=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:43])[CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:42]=[CH:41][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][NH:29][CH2:37][CH2:38][O:39][CH3:40])=[CH:25][N:26]=5)[S:20][C:13]=34)=[C:9]([F:43])[CH:8]=2)=[O:44])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67441817HCID 67441817, compound

Product 1

HCID 67442777HCID 67442777, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 287 (840 mg, 1.35 mmol) in DCM (25 mL) was added TFA (10 mL) and the reaction mixture was stirred for 18 h. The reaction mixture was concentrated, diluted with water and 4N NaOH to pH 13 to form a precipitate which was collected by filtration, washed with water, and dried and purified twice by Biotage (SNAP 50 g; MeOH/DCM: 1/99 to 15/85 over 20 CV) to produce a material that upon trituration with MeOH afforded the title compound 288 (338 mg, 0.65 mmol, 48% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.72 (s, 1H), 8.54-8.49 (m, 2H), 8.30 (s, 1H), 8.19 (d, J=8.2 Hz, 1H), 7.81 (dd, J=8.0, 2.2 Hz, 1H), 7.73 (dd, J=13.5, 2.5 Hz, 1H), 7.38 (t, J=9.1 Hz, 1H), 7.20 (bd, J=8.6 Hz, 1H), 6.63 (d, J=5.5 Hz, 1H), 6.58 (bd, J=2.5 Hz, 1H), 3.37 (t, J=5.7 Hz, 2H), 3.23 (s, 3H), 2.84-2.73 (m, 4H), 2.68 (t, J=5.7 Hz, 2H), 2.59-2.51 (m, 1H), 2.00-1.50 (m, 1H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H).). MS (m/z): 522.6 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water and 4N NaOH to pH 13
  3. customto form a precipitate which
  4. filtrationwas collected by filtration
  5. washwashed with water
  6. customdried
  7. custompurified twice by Biotage (SNAP 50 g; MeOH/DCM: 1/99 to 15/85 over 20 CV)
  8. customto produce a material that upon trituration with MeOH

Sources & evidence

ORD record
ord-1eb40648aecd490ab1769368b6de98dc
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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