HCID 131735630, compound → HCID 118531662, compound

HRID 529836Notes

Reaction equation

HRID 529836 reaction equation
C(OC([NH:8][C@@H:9]([CH2:14][CH2:15][N:16]1[CH:20]=[C:19]([NH:21][C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[CH:31][CH:30]=[N:29][C:28]=23)=[O:23])[C:18]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[O:40][CH:41]([F:43])[F:42])=[N:17]1)[C:10]([O:12][CH3:13])=[O:11])=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH2:8][C@@H:9]([CH2:14][CH2:15][N:16]1[CH:20]=[C:19]([NH:21][C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[CH:31][CH:30]=[N:29][C:28]=23)=[O:23])[C:18]([C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[O:40][CH:41]([F:43])[F:42])=[N:17]1)[C:10]([O:12][CH3:13])=[O:11]

Participants

3

Reactant 1

HCID 131735630HCID 131735630, compound

Product 1

HCID 118531662HCID 118531662, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

The mixture of methyl (2S)-2-[[(tert-butoxy)carbonyl]amino]-4-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]-butanoate (280 mg), in DCM/TFA (15 mL, 2:1) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters)): Column, XSelect CSH Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 0.05% FA and MeCN (24.0% MeCN up to 40.0% in 8 min); Detector, 254/220. 150 mg product was obtained. This resulted in 148.4 mg (73%) of methyl (2S)-2-amino-4-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]butanoate formate as an off-white solid. LCMS (Method 28) [M+H]+=520.1, RT=0.82 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.5, 6.9 Hz), 8.69-8.68 (m, 2H), 8.36 (s, 1H), 7.65-7.61 (m, 2H), 7.45 (d, 1H, J=8.4 Hz), 7.28 (dd, 1H, J=4.2, 7.2 Hz), 7.01 (t, 1H, J=73.2 Hz), 4.40-4.26 (m, 2H), 3.64 (s, 3H), 3.50-3.43 (m, 1H), 2.32-2.18 (m, 1H), 2.11-1.99 (m, 1H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters))

Sources & evidence

ORD record
ord-bcd1163211224eef944b253d3a69843b
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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