4-Methylmorpholine → HCID 178494196, compound

HRID 1466657Notes

Reaction equation

HRID 1466657 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[N:9][C:4]2=[C:3]([C:10]([OH:12])=O)[CH:2]=1.[NH2:13][C:14]1[CH:15]=[N:16][N:17](COCC[Si](C)(C)C)[C:18]=1[C:19]1[C:20]([O:27][CH3:28])=[N:21][CH:22]=[C:23]([CH:26]=1)[C:24]#[N:25].ClC1(OC)N=C(OC)N=CN1.CN1CCOCC1>C(#N)C>[C:24]([C:23]1[CH:26]=[C:19]([C:18]2[C:14]([NH:13][C:10]([C:3]3[CH:2]=[N:1][N:5]4[CH:6]=[CH:7][CH:8]=[N:9][C:4]=34)=[O:12])=[CH:15][NH:16][N:17]=2)[C:20]([O:27][CH3:28])=[N:21][CH:22]=1)#[N:25]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 1910189Pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 66851628HCID 66851628, compoundHCID 178494208HCID 178494208, compound

Product 1

HCID 178494196HCID 178494196, compoundYield 15.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (22.0 mg, 0.135 mmol, 6.56 equiv), 5-(4-amino-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)-6-methoxynicotinonitrile (7.1 mg, 0.020 mmol, 1 equiv), and 2-chloro-2,4-dimethoxy-1,3,5-triazine (23.7 mg, 0.135 equiv, 6.56 equiv) in acetonitrile (2 mL) was added 4-methylmorpholine (23 uL, 0.21 mmol, 10 equiv) at 24° C. After 2 days, the reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (2 mL), saturated aqueous sodium chloride solution (2 mL), and ethyl acetate (5 mL). The organic was separated, and the aqueous was extracted with ethyl acetate (2×5 mL). The combined organic was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was dissolved in ethanol (3 mL) and 6 N aqueous hydrochloric acid (1 mL) and heated to 50° C. After 5 h, the reaction mixture was concentrated in vacuo and purified by preparative HPLC to afford a white solid (1.1 mg, 15% yield). 1H NMR (400 MHz, CDCl3), δ: 9.72 (s, 1H), 8.80 (dd, J=7.0, 1.6 Hz, 1H), 8.74 (s, 1H), 8.66 (m, 1H), 8.54 (d, J=2.2 Hz, 1H), 8.47 (s, 1H), 8.22 (d, J=1.9 Hz, 1H), 7.04 (dd, J=7.0, 4.2 Hz, 1H), 4.11 (s, 3H). LCMS (ESI): M+H=361.1

Workup

  1. customthe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (2 mL), saturated aqueous sodium chloride solution (2 mL), and ethyl acetate (5 mL)
  2. customThe organic was separated
  3. extractionthe aqueous was extracted with ethyl acetate (2×5 mL)
  4. dry with materialThe combined organic was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude material was dissolved in ethanol (3 mL)
  8. waitAfter 5 h
  9. concentrationthe reaction mixture was concentrated in vacuo
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-432d2b013fb34570a1a650cdc8da3d69
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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