p-Toluenesulfonic acid monohydrate → HCID 178497017, compound

HRID 270974Notes

Reaction equation

C(O[C:4](=[O:30])[CH:5]([C:14](=O)[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:17][CH:16]=1)[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)C.[CH3:31][O:32][C:33]([C:35]1[CH:39]=[C:38]([NH2:40])[NH:37][N:36]=1)=[O:34].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClC1C=CC=CC=1>[CH3:31][O:32][C:33]([C:35]1[CH:39]=[C:38]2[NH:40][C:14]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:17][CH:16]=3)=[C:5]([CH2:6][CH2:7][CH:8]3[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]3)[C:4](=[O:30])[N:37]2[N:36]=1)=[O:34]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 71 mg (0.171 mmol) of 2-(4-benzyloxy-benzoyl)-4-cyclohexyl-butyric acid ethyl ester, 24 mg (0.171 mmol) of 5-amino-1H-pyrazole-3-carboxylic acid methyl ester, 7 mg (20 mol %) of p-toluenesulfonic acid monohydrate (PTSA), and 3 mL of chlorobenzene was heated at 120° C. overnight. The reaction mixture was then concentrated to a residue which was purified via reverse-phase chromatography (Gilson) to afford (after lyophilization) desired 5-(4-benzyloxy-phenyl)-6-(2-cyclohexyl-ethyl)-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester as a solid as indicated by LC-MS—calcd for C29H31N3O4 [M++H]+: 486.23, found: 486.2. This material was then converted to 5-(4-benzyloxy-phenyl)-6-(2-cyclohexyl-ethyl)-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid (559) via the well known. LiOH saponification protocol (10% yield over 2 steps); LC-MS—calcd for C28H29N3O4 [M++H]+: 472.22, found: 472.2.

Workup

concentrationThe reaction mixture was then concentrated to a residue which
customwas purified via reverse-phase chromatography (Gilson)

Sources & evidence

ORD record: ord-5f019266785c40528ae4271df93c9164
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449488B2

Reaction notes

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