Ammonia → HCID 57989704, compound

HRID 239365Notes

Reaction equation

HRID 239365 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:32])=[C:21]([NH:25][S:26]([CH:29]3[CH2:31][CH2:30]3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[NH3:33].CO>C(Cl)Cl>[NH2:33][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:32])=[C:21]([NH:25][S:26]([CH:29]3[CH2:31][CH2:30]3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 57989635HCID 57989635, compound

Product 1

HCID 57989704HCID 57989704, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}cyclopropanesulfonamide (125 mg, 0.252 mmol) and 7M ammonia in MeOH (7 mL, 0.49 mmol) was heated in a sealed tube to 80° C. for 2 days. The reaction was diluted with DCM and added silica gel and concentrated. The crude product was chromatographed on silica gel eluting with 100% DCM to 1:1 [DCM:(9:1 EtOAc:MeOH)]. The clean fractions were concentrated to yield the crude product as a yellow solid (62 mg). The crude product was repurified by reverse phase HPLC (a gradient of acetonitrile:water with 0.1% TFA in both). The combined clean fractions were concentrated then partitioned between DCM and saturated NaHCO3. The DCM layer was separated and dried over Na2SO4. The title compound was obtained as a yellow solid (26 mg, 21% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.67 (s, 1H), 7.86 (d, J=5.4 Hz, 1H), 7.49 (td, J=7.4, 2.2 Hz, 1H), 7.11-7.38 (m, 2H), 6.53 (s, 2H), 5.84 (d, J=5.3 Hz, 1H), 3.68 (t, J=4.7 Hz, 4H), 3.43 (t, J=4.7 Hz, 4H), 2.53-2.68 (m, 1H), 0.74-0.92 (m, 4H). MS (ESI): 477.0 [M+H]+.

Workup

  1. additionadded silica gel
  2. concentrationconcentrated
  3. customThe crude product was chromatographed on silica gel eluting with 100% DCM to 1:1 [DCM:(9:1 EtOAc:MeOH)]
  4. concentrationThe clean fractions were concentrated
  5. customto yield the crude product as a yellow solid (62 mg)
  6. customThe crude product was repurified by reverse phase HPLC (a gradient of acetonitrile
  7. concentrationThe combined clean fractions were concentrated
  8. customthen partitioned between DCM and saturated NaHCO3
  9. customThe DCM layer was separated
  10. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-4b5b77a09eba464b80ca47aca9e42789
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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