Diisopropylethylamine → HCID 178520729、化合物

HRID 2378992ノート

反応式

HRID 2378992 の反応式
[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:29])[C:5]=2[NH:4][N:3]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.Cl.[NH:63]1[CH2:68][CH2:67][CH:66]([N:69]2[C:77]3[C:72](=[N:73][CH:74]=[CH:75][CH:76]=3)[NH:71][C:70]2=[O:78])[CH2:65][CH2:64]1>CN(C)C=O>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:63]4[CH2:64][CH2:65][CH:66]([N:69]5[C:77]6[C:72](=[N:73][CH:74]=[CH:75][CH:76]=6)[NH:71][C:70]5=[O:78])[CH2:67][CH2:68]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:29])[C:5]=2[NH:4][N:3]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 178525539HCID 178525539、化合物

生成物 1

HCID 178520729HCID 178520729、化合物収率 71%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(S)-2-(1,4-dichloro-8-oxo-9-(2-(piperidin-1-yl)ethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (74 mg, 0.168 mmol) was dissolved in N,N-dimethylformamide (2.0 ml). N,N-Diisopropylethylamine (120 μl, 0.689 mmol) was added to the mixture followed successively by TBTU (58 mg, 0.181 mmol) and 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one dihydrochloride (58 mg, 0.199 mmol). Reaction stirred at room temperature for 5 hours. Reaction was quenched with 50% acetonitrile-water. Material was purified by reverse phase prep HPLC (water-acetonitrile-trifluoroacetic acid). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as white solid in 71% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.86 (s, 1H) 11.55 (s, 1H) 7.90 (s, 1H) 7.84 (d, J=7.63 Hz, 0.6H) 7.59 (d, J=8.24 Hz, 0.4H) 7.33 (s, 1H) 6.84-7.06 (m, 1 H) 5.22-5.36 (m, 2H) 4.40-4.64 (m, 2H) 4.16 (t, J=14.65 Hz, 1H) 3.80-4.02 (m, 2H) 3.12-3.29(m,3H) 2.95-3.09(m, 1H) 2.84-2.96(m, 1H) 2.62-2.78(m, 1 H) 2.53-2.60 (m, 1H) 2.39-2.49 (m, 1H) 2.01-2.33 (m, 5H) 1.62-1.98 (m, 4H) 1.09-1.22 (m, 6H). High resolution MS m/e (M+H)+=639.2393.

後処理

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMaterial was purified by reverse phase prep HPLC (water-acetonitrile-trifluoroacetic acid)
  5. customAcetonitrile was removed from the fractions by roto-vap
  6. extractionMaterial was extracted twice with ethyl acetate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-bc0bb7eee5104abeb3c50b17a2de615c
出典データセット
uspto-grants-2008_12
特許番号
US07470680B2

反応ノート

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