4-Fluorobenzylamine → (2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 1630311노트

반응식

HRID 1630311 반응식
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:36])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](O)=[O:34])[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][NH2:45])=[CH:40][CH:39]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:36])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](=[O:34])[NH:45][CH2:44][C:41]3[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=3)[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:3])([CH3:4])[CH3:2]

참가 물질

7

반응물 4

HCID 673264-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712583786-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

생성물 1

HCID 71267848(2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate수율 47.6%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (21 mg, 0.042 mmol) and (4-fluorophenyl)methanamine (10.52 mg, 0.084 mmol) in DMF (1 mL) was added DIEA (0.037 mL, 0.210 mmol), HATU (32.0 mg, 0.084 mmol) and DMAP (1.027 mg, 8.41 μmol) and the resulting mixture was stirred at rt for 16 h. At this point LCMS indicated completion of reaction. The reaction mixture was then filtered and purified by prep HPLC to afford (2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (12 mg, 0.020 mmol, 47.1% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ: 7.34-7.30 (m, 2H), 7.23 (t, J=6.4 Hz, 1H), 7.20 (s, 1H), 7.06-6.99 (m, 2H), 6.85 (d, J=10.7 Hz, 1H), 4.96 (s, 1H), 4.67-4.53 (m, 2H), 4.35 (t, J=5.3 Hz, 2H), 4.15 (q, J=7.0 Hz, 2H), 2.79 (s, 3H), 2.76 (t, J=6.6 Hz, 2H), 2.24-2.14 (m, 2H), 1.82 (s, 3H), 1.21 (t, J=7.2 Hz, 3H), 1.17 (s, 9H). LCMS (M+H)=607.4.

후처리

  1. customcompletion of reaction
  2. filtrationThe reaction mixture was then filtered
  3. custompurified by prep HPLC

출처 및 근거

ORD 기록
ord-f088b9fbae494450bc5867f11149146c
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791108B2

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