1,1,3,3-Tetramethylguanidine → HCID 86677250, compound

HRID 1842727Notes

Reaction equation

HRID 1842727 reaction equation
F[P-](F)(F)(F)(F)F.C[N:9]([CH3:25])/[C:10](/[C:16]1[CH:17]=[N:18][N:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=12)=[CH:11]\[CH:12]=[N+:13](C)C.COC(O)C.[NH2:31][C:32]1[C:33]([N:44]2[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]2)=[CH:34][C:35]([O:42][CH3:43])=[C:36]([NH:38]C(N)=N)[CH:37]=1.CN(C)C(N(C)C)=N>COCCO.CCOC(C)=O>[CH3:43][O:42][C:35]1[CH:34]=[C:33]([N:44]2[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]2)[C:32]([NH2:31])=[CH:37][C:36]=1[NH:38][C:25]1[N:9]=[C:10]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=23)[CH:11]=[CH:12][N:13]=1

Participants

7

Reactant 4

HCID 664601,1,3,3-Tetramethylguanidine2×HCID 30156371-MethoxyethanolHCID 136334018HCID 136334018, compound2×HCID 178493014HCID 178493014, compound2×

Product 1

HCID 86677250HCID 86677250, compoundYield 53.4%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of [(Z)-3-(dimethylamino)-3-pyrazolo[1,5-a]pyridin-3-yl-prop-2-enylidene]-dimethyl-ammonium hexafluorophosphate (Intermediate 70, 116 mg, 0.3 mmol) in 2-s methoxyethanol (2 mL) was added dropwise to a stirred solution of 1-(5-amino-2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)guanidine (Intermediate 72, 84 mg, 0.30 mmol) and 1,1,3,3-tetramethylguanidine (0.056 mL, 0.45 mmol) in 2-methoxyethanol (2 mL) at r.t. under N2. The resulting solution was sealed into a microwave tube and heated to 120° C. for 0.25 h then cooled to r.t. Further 1,1,3,3-tetramethylguanidine (0.056 mL, 0.45 mmol) was then added and the mixture was stirred at 120° C. for 0.25 h, then at 140° C. for 0.25 h. The mixture was cooled, diluted with EtOAc (10 mL), and washed with water (2×5 mL). The aqueous solution was extracted with EtOAc (5 mL) and the organic solution was washed with water (2×3 mL). The combined organic solutions were dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1.5-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (69 mg, 53%) as a yellow foam; 1H NMR: 2.25 (3H, d), 2.51 (4H, m), 2.87 (4H, t), 3.73 (3H, s), 4.37 (2H, s), 6.72 (1H, s), 7.07 (1H, m), 7.22 (1H, d), 7.33 (1H, s), 7.40 (1H, m), 7.98 (1H, s), 8.31 (1H, d), 8.52 (1H, d), 8.76 (1H, s), 8.79 (1H, d); m/z: ES+ MH+ 431.

Workup

  1. customThe resulting solution was sealed into a microwave tube
  2. temperaturethen cooled to r.t
  3. waitat 140° C. for 0.25 h
  4. temperatureThe mixture was cooled
  5. washwashed with water (2×5 mL)
  6. extractionThe aqueous solution was extracted with EtOAc (5 mL)
  7. washthe organic solution was washed with water (2×3 mL)
  8. dry with materialThe combined organic solutions were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 1.5-5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-5045354ee59d4381a282169fa31f7fa2
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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