1,2-Dichloroethane → N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide

HRID 1429575노트

반응식

HRID 1429575 반응식
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([C:26]5[CH2:31][CH2:30][N:29]([S:32]([CH2:35][CH2:36][CH2:37][C:38](O)=[O:39])(=[O:34])=[O:33])[CH2:28][CH:27]=5)[CH:23]=[CH:22][C:20]=4[N:21]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:55][CH2:56][C:57]([CH3:60])([OH:59])[CH3:58].CCN(CC)CC>C(Cl)Cl>[OH:59][C:57]([CH3:60])([CH3:58])[CH2:56][NH:55][C:38](=[O:39])[CH2:37][CH2:36][CH2:35][S:32]([N:29]1[CH2:30][CH2:31][C:26]([C:24]2[CH:23]=[CH:22][C:20]3[N:21]=[C:17]([O:16][CH:13]4[CH2:12][CH2:11][N:10]([C:7]5[N:6]=[CH:5][C:4]([CH2:1][CH2:2][CH3:3])=[CH:9][N:8]=5)[CH2:15][CH2:14]4)[S:18][C:19]=3[CH:25]=2)=[CH:27][CH2:28]1)(=[O:34])=[O:33]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 951022-Propanol, 1-amino-2-methyl-HCID 674656774-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoic acid

생성물 1

HCID 71270070N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide수율 68.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoic acid (30 mg, 0.051 mmol), HOBT (10.2 mg, 0.067 mmol), and EDC (12.8 mg, 0.067 mmol) in CH2Cl2 (1 mL) was added 1-amino-2-methylpropan-2-ol (6.9 mg, 0.077 mmol) followed by slow addition of Et3N (0.03 mL, 0.205 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was diluted with CH2Cl2 (2 mL), washed with water (2 mL), then brine. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was recrystallized from 10% water in CH3CN to afford N-(2-hydroxy-2-methylpropyl)-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanamide (24 mg, 0.035 mmol, 68% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.17 (s, 2H), 7.63 (d, J=2.2 Hz, 1H), 7.62 (d, J=4.1 Hz, 1H), 7.38 (dd, J=8.5, 1.7 Hz, 1H), 6.06 (dt, J=3.2, 1.8 Hz, 1H), 6.04-5.99 (m, 1H), 5.45 (tt, J=7.9, 3.8 Hz, 1H), 4.22 (ddd, J=13.3, 6.9, 4.0 Hz, 2H), 4.02 (q, J=2.6 Hz, 2H), 3.73-3.62 (m, 2H), 3.57 (t, J=5.6 Hz, 2H), 3.28 (d, J=6.1 Hz, 2H), 3.10 (t, J=7.0 Hz, 2H), 2.70-2.64 (m, 2H), 2.49 (t, J=6.7 Hz, 2H), 2.41 (t, J=7.4 Hz, 2H), 2.26-2.14 (m, 5H), 1.94 (dtd, J=12.8, 8.3, 3.9 Hz, 2H), 1.62-1.55 (m, 2H), 1.23 (s, 6H), 0.94 (t, J=7.3 Hz, 3H). LCMS (m/z)=657 (M+H)+.

후처리

  1. washwashed with water (2 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was recrystallized from 10% water in CH3CN

출처 및 근거

ORD 기록
ord-d870c29b8c724e8f9fc90abd57a4ac02
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940716B2

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