Fasudil → 5-({1-[(2R)-2-propyloctanoyl]azepan-4-yl}sulfonyl)quinoline

HRID 1727338

反応式

HRID 1727338 の反応式
[CH2:1]([C@H:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([OH:7])=O)[CH2:2][CH3:3].CN(C(ON1N=N[C:24]2[CH:25]=[CH:26][CH:27]=N[C:23]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[N:39]1[CH2:44][CH2:43]O[CH2:41][CH2:40]1.C1C=C2[C:52](=[C:53]([S:55](N3CCNCCC3)(=[O:57])=[O:56])[CH:54]=1)[CH:51]=[CH:50][N:49]=[CH:48]2.C(O)(C(F)(F)F)=O>CN(C=O)C.CO>[CH2:1]([C@H:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([N:49]1[CH2:50][CH2:51][CH2:52][CH:53]([S:55]([C:25]2[CH:26]=[CH:27][CH:41]=[C:40]3[C:24]=2[CH:23]=[CH:43][CH:44]=[N:39]3)(=[O:56])=[O:57])[CH2:54][CH2:48]1)=[O:7])[CH2:2][CH3:3]

参加物

8

反応物 5

HCID 3547FasudilHCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 208925(R)-(-)-2-propyloctanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

生成物 1

HCID 690404485-({1-[(2R)-2-propyloctanoyl]azepan-4-yl}sulfonyl)quinoline

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

(R)-2-propyloctanoic acid (100 mg, 0.48 mmol) was dissolved in 1 mL DMF. HATU (201 mg, 0.53 mmol) and NMM (64 μL, 0.58 mmol) were added and the solution was stirred for 5 min. Fasudil (154 mg, 0.53 mmol) was added and the solution was stirred for 2 h at rt. The reaction was quenched with TFA (48 μL, 0.63 mmol) and MeOH (1 mL) and purified by preparative HPLC (50% to 100% ACN/water) to give the product (Example 5) as a white solid. 1H-NMR (500 MHz, CDCl3) δ 9.81 (s, 1H), 8.94 (d, 1H), 8.70 (d, 1H), 8.54-8.60 (m, 2H), 7.98 (t, 1H), 7.28 (s, 1H), 3.71-3.76 (m, 4H), 3.45-3.48 (m, 4H), 2.56-2.58 (m, 1H), 2.04-2.07 (m, 2H), 1.59-1.65 (m, 2H), 1.43-1.44 (m, 2H), 1.26-1.29 (m, 10H), 0.86-0.91 (m, 6H). MS (ESI) 460 (M+H).

後処理

  1. stirringthe solution was stirred for 2 h at rt
  2. custompurified by preparative HPLC (50% to 100% ACN/water)
  3. customto give the product (Example 5) as a white solid

出典と根拠

ORDレコード
ord-05d3ae90157a49d084a8e9d73f893195
出典データセット
uspto-grants-2009_02
特許番号
US07495029B2

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