4-Methylmorpholine → (R/S)-2-hydroxy-N-(2-hydroxy-2-methylpropyl)-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

HRID 77177

반응식

HRID 77177 반응식
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[CH:18]=[N:19][N:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:21]=3[C:22]([F:25])([F:24])[F:23])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[NH2:32][CH2:33][C:34]([CH3:37])([OH:36])[CH3:35].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:16]=[C:15]([C:17]3[CH:18]=[N:19][N:20]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:21]=3[C:22]([F:25])([F:23])[F:24])[O:14][N:13]=2)=[CH:10][CH:11]=1)[C:3]([NH:32][CH2:33][C:34]([OH:36])([CH3:37])[CH3:35])=[O:5]

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 951022-Propanol, 1-amino-2-methyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67460691(R/S)-2-hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

생성물 1

HCID 53495666(R/S)-2-hydroxy-N-(2-hydroxy-2-methylpropyl)-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide수율 39.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(R/S)-2-Hydroxy-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-VII, 40 mg, 0.093 mmol), 1-amino-2-methylpropan-2-ol (12.43 mg, 0.139 mmol), 4-methylmorpholine (37.6 mg, 0.372 mmol), and HATU (45.9 mg, 0.121 mmol) were dissolved in DMF (1 mL). It was stirred for 20 min and was then purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% methanol to 100% methanol over 10 min, 20 mL/min, 220 nM, product retention=11.2 min) to provide (R/S)-2-hydroxy-N-(2-hydroxy-2-methylpropyl)-2-(4-(5-(1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (20 mg, 0.036 mmol, 39.2% yield): LCMS=502.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.48 (1 H, s), 8.13 (2 H, d, J=8.35 Hz), 7.52-7.76 (7 H, m), 5.16 (1 H, s), 3.25 (2 H, s), 1.17 (3 H, s), 1.14 (3 H, s); HPLC peak RT=7.3 min (Method A).

후처리

  1. customwas then purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% methanol to 100% methanol over 10 min, 20 mL/min, 220 nM, product retention=11.2 min)

출처 및 근거

ORD 기록
ord-d54183e22a3148aa8915803a1b41ac99
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835470B2

연결된 노트

불러오는 중…