Water → HCID 67441768, compound

HRID 1400826Notes

Reaction equation

HRID 1400826 reaction equation
[CH:1]1([NH:4][C:5](=[O:45])[NH:6][C:7]2[CH:43]=[CH:42][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][N:28]6[CH2:32][CH2:31][C@H:30]([NH:33]C(=O)OC(C)(C)C)[C:29]6=[O:41])=[CH:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:44])[CH:8]=2)[CH2:3][CH2:2]1.O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:33][C@H:30]1[CH2:31][CH2:32][N:28]([CH2:27][C:24]2[CH:23]=[CH:22][C:21]([C:19]3[S:20][C:13]4[C:14](=[N:15][CH:16]=[CH:17][C:12]=4[O:11][C:10]4[CH:42]=[CH:43][C:7]([NH:6][C:5]([NH:4][CH:1]5[CH2:3][CH2:2]5)=[O:45])=[CH:8][C:9]=4[F:44])[CH:18]=3)=[N:26][CH:25]=2)[C:29]1=[O:41]

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 67442421HCID 67442421, compound

Product 1

HCID 67441768HCID 67441768, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 107 (120 mg, 0.19 mmol) in DCM (20 mL) was added water (0.5 mL) and TFA (4 mL, 51.9 mmol). The reaction mixture was stirred at RT for 6 h, concentrated, diluted with ethyl acetate, and washed with 1N NaOH. The organic phase was collected and the aqueous phase was re-extracted with ethyl acetate. The combined organic layers (a lot of unsoluble material stayed on the walls of the separatory funnel which was dissolved in MeOH and combined with the organic layers) were concentrated. A 1N NaOH solution was added; the suspension was stirred for 30 min and the solid was collected by filtration. The crude product was purified by Biotage (SNAP 50 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 40/60 over 20 CV), to afford the title compound 108 (77 mg, 0.14 mmol, 76% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.77 (s, 1H), 8.55-8.51 (m, 2H), 8.36 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.81 (dd, J=8.0, 2.0 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.2 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 6.65 (d, J=5.6 Hz, 1H), 6.60 (d, J=2.4 Hz, 1H), 4.52 (d, J=15.2 Hz, 1H), 4.45 (d, J=15.2 Hz, 1H), 4.15-3.65 (m, 214), 3.58 (t, J=8.8 Hz, 1H), 3.30-3.14 (m, 2H), 2.59-2.52 (m, 1H), 2.34-2.23 (m, 1H), 1.77-1.65 (m, 1H), 0.68-0.62 (m, 2H), 0.45-0.37 (m, 2H). MS (m/z): 533.6 (M+H).

Workup

  1. concentrationconcentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with 1N NaOH
  4. customThe organic phase was collected
  5. extractionthe aqueous phase was re-extracted with ethyl acetate
  6. dissolutionwas dissolved in MeOH
  7. concentrationwere concentrated
  8. additionA 1N NaOH solution was added
  9. stirringthe suspension was stirred for 30 min
  10. filtrationthe solid was collected by filtration
  11. customThe crude product was purified by Biotage (SNAP 50 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 40/60 over 20 CV)

Sources & evidence

ORD record
ord-e8998952b2d948f8837f74ce7eaa7af4
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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