Triethylamine → HCID 21865179, compound

HRID 859039Notes

Reaction equation

HRID 859039 reaction equation
[CH:1]1([CH2:7][C:8]([OH:10])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[C:28]1[N:33]=[CH:32][N:31]=[C:30]([O:34][C:35]2[C:40]3[N:41]=[C:42]([NH:44][C:45](=[O:47])[CH3:46])[S:43][C:39]=3[CH:38]=[CH:37][CH:36]=2)[CH:29]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.CC(C)=O>[C:45]([NH:44][C:42]1[S:43][C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([O:34][C:30]3[N:31]=[CH:32][N:33]=[C:28]([C:19]4[CH:20]=[CH:21][C:22]([C:24]([F:27])([F:25])[F:26])=[CH:23][C:18]=4[NH:17][C:8](=[O:10])[CH2:7][CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)[CH:29]=3)[C:40]=2[N:41]=1)(=[O:47])[CH3:46]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 21363Cyclohexaneacetic acidHCID 65578Oxalyl chlorideHCID 21865046N-(4-(6-(2-Amino-4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

Product 1

HCID 21865179HCID 21865179, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of cyclohexylacetic acid (0.16 g, 1.1 mmol, Aldrich) in CH2Cl2 (5 mL) and DMF (2 drops) was added oxalyl chloride (0.84 mL, 1.7 mmol, 2 M solution in CH2Cl2, Aldrich) dropwise. After the addition was complete and gas evolution ceased, the reaction mixture was heated at 40° C. for 30 min. The excess oxalyl chloride and CH2Cl2 was evaporated in vacuum to provide a yellow oil. The oil was added dropwise to a solution of N-{4-[6-(2-amino-4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide, (Example 151), (0.25 g, 0.56 mmol) in acetone (15 mL) and triethylamine (0.20 mL, 1.7 mmol, Aldrich) at room temperature. The reaction mixture was stirred for 16 h and then concentrated in vacuum. The residue was dissolved in EtOAc (10 mL) and washed with satd NaHCO3 (2×20 mL), dried over Na2SO4, filtered and concentrated in vacuum. Purification by silica gel chromatography (1:1:0.5 CH2Cl2/hexanes/EtOAc) provided the title compound as a white crystalline solid. Mp: 288–289° C. MS (ESI, pos. ion) m/z: 570 (M+1).

Workup

  1. additionAfter the addition
  2. customThe excess oxalyl chloride and CH2Cl2 was evaporated in vacuum
  3. customto provide a yellow oil
  4. concentrationconcentrated in vacuum
  5. dissolutionThe residue was dissolved in EtOAc (10 mL)
  6. washwashed with satd NaHCO3 (2×20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuum
  10. customPurification by silica gel chromatography (1:1:0.5 CH2Cl2/hexanes/EtOAc)

Sources & evidence

ORD record
ord-0e49e59929b34cbeaa2bada7f658f6ba
Source dataset
uspto-grants-2006_12
Patent number
US07148221B2

Reaction notes

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