Diisopropylethylamine → (S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(pyrrolidin-1-ylmethyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone

HRID 1423153노트

반응식

HRID 1423153 반응식
Cl.Cl.[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([N:17]3[CH2:22][CH2:21][NH:20][C@@H:19]([CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[CH3:38][C:39]1[NH:43][N:42]=[C:41]([CH2:44][C:45](O)=[O:46])[N:40]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([N:17]3[CH2:22][CH2:21][N:20]([C:45](=[O:46])[CH2:44][C:41]4[N:40]=[C:39]([CH3:38])[NH:43][N:42]=4)[C@@H:19]([CH2:23][N:24]4[CH2:25][CH2:26][CH2:27][CH2:28]4)[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70194772-(3-methyl-1H-1,2,4-triazol-5-yl)acetic acidHCID 131732229(S)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(pyrrolidin-1-ylmethyl)piperazine, dihydrochloride2회

생성물 1

HCID 67291108(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(pyrrolidin-1-ylmethyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone수율 64%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A solution of (S)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(pyrrolidin-1-ylmethyl)piperazine, dihydrochloride (Example 40, Compound 128) (173 mg, 0.40 mmol) in CH2Cl2 (1 mL) and DMF (1 mL) was treated with diisopropylethylamine (348 uL, 2.0 mmol), 2-(5-methyl-1H-1,2,4-triazol-3-yl)acetic acid CAS [720706-28-5] (68 mg, 0.48 mmol) followed by HBTU (162 mg, 0.48 mmol). The reaction mixture was stirred for 16 h after which time the mixture was partitioned between CH2Cl2 (3 mL) and a saturated aqueous solution of NaHCO3 (2 mL). The organic portion was further washed with NaHCO3 (2×3 mL) followed by brine (3 mL). The organic portion was then dried over MgSO4, filtered, and evaporated to afford quenched with evaporated and the residue purified by silica gel flash chromatography with 5% MeOH/EtOAc the 10% MeOH/EtOAc containing 1% NH4OH as eluant to afford product as a foam (123 mg, 64%). LC/MS (Method B) 2.18 min, [M+1]+ 483. Potency class C.

후처리

  1. customwas partitioned between CH2Cl2 (3 mL)
  2. washThe organic portion was further washed with NaHCO3 (2×3 mL)
  3. dry with materialThe organic portion was then dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford
  7. customquenched
  8. customwith evaporated
  9. customthe residue purified by silica gel flash chromatography with 5% MeOH/EtOAc the 10% MeOH/EtOAc containing 1% NH4OH as eluant

출처 및 근거

ORD 기록
ord-1791ce914fad425d8903ee2b45d2272d
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927546B2

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