Diisopropylethylamine → 3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1476539ノート

反応式

HRID 1476539 の反応式
C([O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[C:10](C3C=CC(C(O)=O)=CC=3)=[N:9][C@@H:8]3[CH2:25][CH2:26][S:27][CH2:28][C@@H:7]3[C:6]=2[CH:5]=1)C.[B-](F)(F)(F)F.CCO[C:37]([C:39]([C:49]#N)=NOC(N(C)C)=[N+](C)C)=[O:38].[CH:51]1C=N[C:54]2N(O)N=N[C:53]=2[CH:52]=1.[CH3:61][CH2:62]N(C(C)C)C(C)C.FC(F)(F)C(O)=O.[CH3:77][O:78][CH2:79][N:80]1[N:84]=[N:83][C:82]([CH2:85][N:86]2[C:91]3[CH:92]=[C:93]([C:95]4[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=4)[S:94][C:90]=3[C:89](=[O:101])[N:88]([CH:102]3[CH2:107][CH2:106][NH:105][CH2:104][CH2:103]3)[C:87]2=[O:108])=[N:81]1>C(Cl)Cl>[CH2:61]([O:3][C:4]1[C:13]([O:14][CH3:15])=[CH:12][C:11]2[C:10]([C:52]3[CH:51]=[CH:49][C:39]([C:37]([N:105]4[CH2:106][CH2:107][CH:102]([N:88]5[C:89](=[O:101])[C:90]6[S:94][C:93]([C:95]7[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=7)=[CH:92][C:91]=6[N:86]([CH2:85][C:82]6[N:83]=[N:84][N:80]([CH2:79][O:78][CH3:77])[N:81]=6)[C:87]5=[O:108])[CH2:103][CH2:104]4)=[O:38])=[CH:54][CH:53]=3)=[N:9][C@@H:8]3[CH2:7][CH2:28][S:27][CH2:26][C@@H:25]3[C:6]=2[CH:5]=1)[CH3:62]

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAt2 回HCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate2 回HCID 67258448HCID 67258448、化合物HCID 672590924-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid2 回

生成物 1

HCID 532471203-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (251 mg; compound C10), TOTU (270 mg), HOAT (129 mg), DIPEA (327 mg) in DCM (8 ml) is stirred for 1 h at RT. To this mixture 1-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenyl-3-(piperidin-4-yl)thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione trifluoroacetate (359 mg; compound B25) is added and the reaction mixture is stirred for additional 3 h at RT. Additional 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoic acid (125 mg; compound C10), TOTU (207 mg) and HOAT (86 mg) are added to drive the reaction to completion. After stirring for 1 h at RT the reaction is quenched by addition of DCM (10 ml) and a saturated aqueous solution of sodium bicarbonate (10 ml). The organic phase is separated and the aqueous phase is extracted with DCM (5 ml). The combined organic phases are applied to a phase separator and the solvent is removed under vacuum. The resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: cyclohexane/EtOAc, 100/0 to 0/100 (v/v)] to yield the title compound as a solid.

後処理

  1. stirringthe reaction mixture is stirred for additional 3 h at RT
  2. customthe reaction to completion
  3. stirringAfter stirring for 1 h at RT the reaction
  4. customis quenched by addition of DCM (10 ml)
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted with DCM (5 ml)
  7. customthe solvent is removed under vacuum
  8. customThe resulting residue is purified by flash column chromatography [amino phase silica gel, eluation gradient: cyclohexane/EtOAc, 100/0 to 0/100 (v/v)]

出典と根拠

ORDレコード
ord-fcd38bdffba6414b868275e818fe30ef
出典データセット
uspto-grants-2015_04
特許番号
US09018175B2

反応ノート

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