Hydrochloric Acid → phenylmethyl [2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamate

HRID 1910029

反応式

HRID 1910029 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([N:43](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:27][CH:28]=[C:29]([CH2:30][CH2:31][NH:32][C:33]([O:35][CH2:36][C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)=[O:34])[C:24]=4[O:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].Cl.O1CCOCC1>>[C:37]1([CH2:36][O:35][C:33](=[O:34])[NH:32][CH2:31][CH2:30][C:29]2[C:24]3[O:23][CH:22]=[C:21]([C:17]4[CH:16]=[C:15]5[C:20](=[CH:19][CH:18]=4)[N:12]([C:10](=[O:11])[CH2:9][C:3]4[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=4[F:1])[CH2:13][CH2:14]5)[C:25]=3[C:26]([NH2:43])=[N:27][CH:28]=2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

参加物

4

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66823788bis(1,1-dimethylethyl) {3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-[2-({[(phenylmethyl)oxy]carbonyl}amino)ethyl]furo[3,2-c]pyridin-4-yl}imidodicarbonate

生成物 1

HCID 69939762phenylmethyl [2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamate収率 85.3%

実験手順

A mixture of bis(1,1-dimethylethyl) {3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-[2-({[(phenylmethyl)oxy]carbonyl}amino)ethyl]furo[3,2-c]pyridin-4-yl}imidodicarbonate (149 mg, 0.190 mmol) and 4.0 M HCl in dioxane (2.0 mL, 8.00 mmol) was stirred at room temperature under Nitrogen for 4 hr. The crude reaction mixture was then concentrated in vacuo and azeotroped once with acetonitrile. The residue was taken up in DCM and passed through a PL-HCO3 MP-resin cartridge, rinsing with more DCM. The filtrate was then concentrated in vacuo to give the free base of phenylmethyl[2-(4-amino-3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-7-yl)ethyl]carbamate (105 mg, 0.162 mmol, 85% yield) as an off-white foam (purity estimated at 90%). LC/MS (ES) m/z=583.6 [M+H]+. 1H NMR (400 MHz, DMSO-d6) d 2.86 (t, J=7.07 Hz, 2H), 3.22-3.34 (m, 4H), 3.96 (s, 2H), 4.31 (t, J=8.34 Hz, 2H), 5.02 (s, 2H), 5.38 (s, 2H), 7.14-7.44 (m, 12H), 7.68 (s, 1H), 7.93 (s, 1H), 8.12 (d, J=8.34 Hz, 1H).

後処理

  1. customThe crude reaction mixture
  2. concentrationwas then concentrated in vacuo
  3. customazeotroped once with acetonitrile
  4. washrinsing with more DCM
  5. concentrationThe filtrate was then concentrated in vacuo

出典と根拠

ORDレコード
ord-2fab4b7a7fbd4f66b994c35599d0d281
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

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