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Triethylamine → (S)-N-(1-(4-chlorophenyl)-5-isopropyl-1H-pyrazol-4-yl)-2-(2-methyl-4-(trifluoromethyl)-1H-imidazol-1-yl)propanamide

HRID 1754377
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HRID 1754377 반응식
[CH3:1][C:2]1[N:3]([CH:13]([CH2:19]C=C)[C:14]([O:16]CC)=O)[C:4](C=C)=[C:5]([C:7]([F:10])([F:9])[F:8])[N:6]=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[C:33]([CH:34]([CH3:36])[CH3:35])=[C:32]([NH2:37])[CH:31]=[N:30]2)=[CH:25][CH:24]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([N:29]2[C:33]([CH:34]([CH3:35])[CH3:36])=[C:32]([NH:37][C:14](=[O:16])[C@@H:13]([N:3]3[CH:4]=[C:5]([C:7]([F:8])([F:9])[F:10])[N:6]=[C:2]3[CH3:1])[CH3:19])[CH:31]=[N:30]2)=[CH:27][CH:28]=1
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참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 664259211-(4-chlorophenyl)-5-(propan-2-yl)-1H-pyrazol-4-amineHCID 86724377Ethyl 2-[2-methyl-4-(trifluoromethyl)-5-vinyl-imidazol-1-yl]pent-4-enoate

생성물 1

HCID 76902964
(S)-N-(1-(4-chlorophenyl)-5-isopropyl-1H-pyrazol-4-yl)-2-(2-methyl-4-(trifluoromethyl)-1H-imidazol-1-yl)propanamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of the acid intermediate from step d (23.6 mg, 0.1 mmol) and 1-(4-chlorophenyl)-5-isopropyl-1H-pyrazol-4-amine (16.6 mg, 0.064 mmol) in DMF (0.5 mL) was added Et3N (20 μL, 0.13 mmol) and HATU (31.6 mg, 0.083 mmol). After stirring 35 min, the slurry was concentrated under reduced pressure and the residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent). The residue was neutralized and salted with HCL to provide the titled compound hydrochloride salt as a colorless solid (12.3 mg). 1H NMR (400 MHz, CD3OD) δ 8.28 (d, J=1.6 Hz, 1H), 7.63 (s, 1H), 7.57 (ddd, J=9.7, 5.1, 3.1 Hz, 2H), 7.41 (ddd, J=9.7, 5.0, 3.1 Hz, 2H), 5.38 (q, J=7.0 Hz, 1H), 3.03 (hept, J=7.0 Hz, 1H), 2.65 (s, 3H), 1.91 (d, J=7.0 Hz, 3H), 1.23 (d, J=7.1 Hz, 3H), 1.22 (d, J=7.0 Hz, 3H); MS: (ES) m/z calculated for C20H22ClF3N5O [M+H]+ 440.1, found 439.9. Retention time on chiral HPLC: 5.9 min (RegisPack cat#783104, 25 cm×4.6 mm, 5 micron; eluent: 0.1% diethylamine/IPA, 1.0 ml/min). The er is determined to be 20:1 with the (R)-enantiomer having a retentime of 3.4 min. Absolute configuration of the (R)-enantiomer was confirmed by an independent synthesis from methyl (L)-lactate.

후처리

  1. concentrationthe slurry was concentrated under reduced pressure
  2. customthe residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

출처 및 근거

ORD 기록
ord-bdb8a8c065664c3c9dfc983bc7495534
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09169248B2

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