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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
ノート
印刷プレビュー

反応式

HRID 1754377 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-bdb8a8c065664c3c9dfc983bc7495534
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09169248B2

反応ノート

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