Ammonium Hydroxide → HCID 57989917, compound

HRID 239360Notes

Reaction equation

HRID 239360 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]([CH2:18]C)[CH2:14][CH2:15][O:16][CH3:17])=[N:10][C:9]=2[C:20]2[C:21]([F:36])=[C:22]([NH:26][S:27]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)(=[O:29])=[O:28])[CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:4][N:3]=1.[NH4+:37].[OH-]>O.Cl.C(Cl)Cl>[NH2:37][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:20]2[C:21]([F:36])=[C:22]([NH:26][S:27]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)(=[O:28])=[O:29])[CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 14923Ammonium HydroxideHCID 86636584HCID 86636584, compound

Product 1

HCID 57989917HCID 57989917, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

N-[3-(5-(2-Chloro-4-pyrimidinyl)-2-{ethyl[2-(methyloxy)ethyl]amino}-1,3-thiazol-4-yl)-2-fluorophenyl]cyclohexanesulfonamide (148 mg, 0.275 mmol) was suspended in NH4OH (4 mL) and heated in microwave reactor at 120° C. for 48 min. The reaction was diluted with water and neutralized with 5% aqueous HCl and solid formed. A solid was diluted with DCM and water. The organic layer was dried over Na2SO4, filtered, 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 combined and concentrated. The product was triturated in diethyl ether and filtered to obtain the title compound as a yellow powder (58 mg, 41% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.67 (s, 1H), 7.87 (d, J=5.3 Hz, 1H), 7.43-7.62 (m, 1H), 7.09-7.41 (m, 2H), 6.35-6.74 (m, 2H), 5.80 (d, J=5.3 Hz, 1H), 3.68 (t, J=4.6 Hz, 4H), 3.43 (t, J=4.6 Hz, 4H), 2.81-3.02 (m, 1H), 1.69 (d, J=12.5 Hz, 2H), 1.51 (br. s., 1H), 1.33 (qd, J=12.1, 2.2 Hz, 2H), 0.89-1.22 (m, 5H). MS (ESI): 518.9 [M+H]+.

Workup

  1. customformed
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. additionadded silica gel
  5. concentrationconcentrated
  6. customThe crude product was chromatographed on silica gel eluting with 100% DCM to 1:1 [DCM:(9:1 EtOAC:MeOH)]
  7. concentrationconcentrated
  8. customThe product was triturated in diethyl ether
  9. filtrationfiltered

Sources & evidence

ORD record
ord-7fee4af2bd694bc7a21df23c6ab57bda
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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