Cyclopropanecarbonyl chloride → HCID 67064651, compound

HRID 1409254Notes

Reaction equation

HRID 1409254 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]3[N:14]=[C:15]([CH3:17])[CH:16]=[C:12]3[N:11]=[C:10]([NH:18][C:19](=[O:30])[C:20]3[CH:25]=[CH:24][C:23]([C:26]([OH:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=3)[CH:9]=2)[CH2:4][CH2:3]1.[CH:31]1([C:34](Cl)=[O:35])[CH2:33][CH2:32]1>N1C=CC=CC=1>[CH:31]1([C:34]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8]3[N:13]4[N:14]=[C:15]([CH3:17])[CH:16]=[C:12]4[N:11]=[C:10]([NH:18][C:19](=[O:30])[C:20]4[CH:21]=[CH:22][C:23]([C:26]([OH:29])([CH3:27])[CH3:28])=[CH:24][CH:25]=4)[CH:9]=3)[CH2:4][CH2:3]2)=[O:35])[CH2:33][CH2:32]1

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 67064491HCID 67064491, compound

Product 1

HCID 67064651HCID 67064651, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

N-(7-(4-aminopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (6B, 250 mg, 0.612 mmol) was dissolved in anhydrous pyridine (1.2 mL). Cyclopropanecarbonyl chloride (61 μL, 0.673 mmol) was added at 0° C., and the mixture was stirred in an ice bath and warmed to room temperature. The reaction was complete as determined by LCMS analysis. The reaction was then quenched with saturated NaHCO3; pyridine was removed in vacuo and the residue was extracted with EtOAc. Purification by preparatory HPLC (30-50% MeCN/H2O gradient+0.01% TFA) provided the titled compound as a white solid (22 mg, 8%). Melting point (214.0-214.1° C.). 1H NMR (DMSO-d6) δ: 10.83 (s, 1H), 8.13 (d, J=7.8 Hz, 1H), 7.99 (d, J=8.8 Hz, 2H), 7.59 (d, J=8.6 Hz, 2H), 7.36 (s, 1H), 6.15 (s, 1H), 4.35 (br. s., 2H), 3.93 (br. s., 2H), 3.15-3.26 (m, 2H), 2.38 (t, 3H), 1.92 (d, J=9.9 Hz, 2H), 1.48-1.71 (m, 3H), 1.45 (s, 6H), 0.55-0.73 (m, 4H). ESI-MS: m/z 477.0 (M+H)+.

Workup

  1. customThe reaction was then quenched with saturated NaHCO3
  2. custompyridine was removed in vacuo
  3. extractionthe residue was extracted with EtOAc
  4. customPurification by preparatory HPLC (30-50% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-318a2cb78b0a409ebb9744f362e57399
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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