Acetic Acid → 6-[4-(3-Morpholin-4-ylpropyl)phenyl]-3-phenylpyrazolo[1,5-a]pyrimidine

HRID 856006Notes

Reaction equation

HRID 856006 reaction equation
[C:1]1([C:7]2[CH:8]=[N:9][N:10]3[CH:15]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH:24]=O)=[CH:18][CH:17]=4)[CH:13]=[N:12][C:11]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[N:26]1([CH2:24][CH2:23][CH2:22][C:19]2[CH:18]=[CH:17][C:16]([C:14]3[CH:13]=[N:12][C:11]4[N:10]([N:9]=[CH:8][C:7]=4[C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:15]=3)=[CH:21][CH:20]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 586916073-[4-(3-Phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]propanal

Product 1

HCID 98010156-[4-(3-Morpholin-4-ylpropyl)phenyl]-3-phenylpyrazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 3-[4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]propanal (2-5, 150 mg, 0.458 mmol, 1 equiv), morpholine (0.048 mL, 0.55 mmol, 1.2 equiv), acetic acid (0.026 mL, 0.55 mmol, 1.0 equiv), and sodium triacetoxyboro-hydride (116 mg, 0.547 mmol, 1.20 equiv) in dichloroethane (8 mL) was stirred in the presence of 4 angstrom molecular sieves for 15 minutes. The reaction mixture was partitioned between saturated sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (50% hexane in chloroform saturated with ammonia gas, grading to 100% chloroform saturated with ammonia gas) to give 6-[4-(3-morpholin-4-ylpropyl)phenyl]-3-phenylpyrazolo[1,5-a]pyrimidine (2-6) as a yellow solid (mp=147-149° C.). 1H NMR (400 MHz, CDCl3) δ8.82 (s, 2H), 8.45 (s, 1H), 8.06 (br d, 2H, J=7.8 Hz), 7.53 (d, 2H, J=8.2 Hz), 7.47 (t, 2H, J=7.8 Hz), 7.35 (d, 2H, J=8.2 Hz), 7.29 (t, 1H, J=7.8 Hz), 3.73 (m, 4H), 2.73 (t, 2H, J=7.5 Hz), 2.46 (m, 4H), 2.40 (t, 2H, J=7.2 Hz), 1.87 (pentet, 2H, J=7.7 Hz).

Workup

  1. customThe reaction mixture was partitioned between saturated sodium bicarbonate solution (100 mL) and ethyl acetate (100 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (50% hexane in chloroform saturated with ammonia gas, grading to 100% chloroform saturated with ammonia gas)

Sources & evidence

ORD record
ord-0ff7f0f2f2d34a5b966f3434bcdeaeee
Source dataset
uspto-grants-2007_08
Patent number
US07262199B2

Reaction notes

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