Methanamine, N-methoxy-, hydrochloride (1:1) → 4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid methoxy-methyl-amide

HRID 63761Notes

Reaction equation

HRID 63761 reaction equation
[CH2:1]([N:8]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:12][C:11]([CH3:21])([CH3:20])[N:10]2[N:22]=[CH:23][C:24]([C:25](O)=[O:26])=[C:9]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)O.C(N(C(C)C)CC)(C)C.Cl.[CH3:53][O:54][NH:55][CH3:56]>O.CN1C(=O)CCC1>[CH3:53][O:54][N:55]([CH3:56])[C:25]([C:24]1[CH:23]=[N:22][N:10]2[C:11]([CH3:21])([CH3:20])[CH2:12][CH:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:9]=12)=[O:26]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 21864398Tetramethyluronium hexafluorophosphateHCID 57631694HCID 57631694, compound

Product 1

HCID 576317744-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid methoxy-methyl-amideYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To a 5 mL NMP solution containing 0.72 g (1.99 mmol) of 2 was added 0.91 g (2.39 mmol) of O-7-azabenzotriazolo-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU) and 0.416 mL (2.39 mmol) of diisopropylethylamine. After stirring for 30 min, 0.233 g (2.39 mmol) of O,N-dimethyl-hydroxylamine hydrochloride was added and the reaction heated to 50° C. After 1 h, the reaction mixture was poured into water and extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give a crude oil. Purification of this oil by flash chromatography eluting with a 60 to 50% hexanes/AcOEt gradient gave 0.65 g (81%) of the title compound as a light golden colored solid. 1H NMR (CDCl3) δ 1.37 (s, 3H), 1.56 (s, 3H), 2.06-2.16 (m, 2H), 3.25 (s, 3H), 3.49 (s, 3H), 3.90 (d, J=16.0 Hz, 1H), 4.45 (dd, J=5.1, 11.3 Hz, 1H), 5.06 (d, J=16.2 Hz, 1H), 6.98 (dd, J=1.8, 6.1 Hz, 2H), 7.20-7.24 (m, 3H), 7.30-7.34 (m, 1H), 7.37-7.41 (m, 4H), 7.74 (s, 1H). MS Calcd.: 404. Found: 405 (M+H).

Workup

  1. waitAfter 1 h
  2. extractionextracted with AcOEt
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a crude oil
  8. customPurification of this oil by flash chromatography
  9. washeluting with a 60 to 50% hexanes/AcOEt gradient

Sources & evidence

ORD record
ord-2dab56481fbc489abe90a850fb17d86c
Source dataset
uspto-grants-2016_09
Patent number
US09447100B2

Reaction notes

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