Methylamine → (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[4-(methylamino)-4-oxobutoxy]benzyl}propylcarbamate

HRID 1253963ノート

反応式

HRID 1253963 の反応式
[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([O:9][C:10]([NH:12][C@H:13]([C@H:28]([OH:47])[CH2:29][N:30]([S:35]([C:38]2[CH:46]=[CH:45][C:41]3[O:42][CH2:43][O:44][C:40]=3[CH:39]=2)(=[O:37])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:14][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=O)=[CH:17][CH:16]=2)=[O:11])[CH2:2]1.[CH:48]([N:51](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN>CN(C=O)C.CCO>[O:42]1[C:41]2[CH:45]=[CH:46][C:38]([S:35]([N:30]([CH2:31][CH:32]([CH3:33])[CH3:34])[CH2:29][C@@H:28]([OH:47])[C@@H:13]([NH:12][C:10](=[O:11])[O:9][C@@H:3]3[C@H:4]4[C@H:5]([O:6][CH2:7][CH2:8]4)[O:1][CH2:2]3)[CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:19][CH2:20][CH2:21][CH2:22][C:23]([NH:51][CH3:48])=[O:25])=[CH:26][CH:27]=3)(=[O:36])=[O:37])=[CH:39][C:40]=2[O:44][CH2:43]1

参加物

7

反応物 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57945104HCID 57945104、化合物

生成物 1

HCID 60097292(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxy-1-{4-[4-(methylamino)-4-oxobutoxy]benzyl}propylcarbamate収率 61.2%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 35 mg (0.052 mmol) of 4-(4-{(2S,3R)-2-({[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl}amino)-4-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-3-hydroxybutyl}phenoxy)butanoic acid and 27 μL (0.16 mmol) of N,N-diisopropylethylamine in 1 mL of anhydrous DMF was treated with 49 mg (0.13 mmol) of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU). The resulting solution was stirred at RT for 15 minutes and was then treated with 0.5 mL of 8M MeNH2 in EtOH. After 18 hours TLC indicated the reaction to be complete. The solution was concentrated to dryness at reduced pressure and the residue subjected to flash chromatography (SiO2, 95:5 CH2Cl2/MeOH) to afford 22 mg (61%) of the desired compound as a white powder. 1H NMR (CDCl3): 7.37 (d, 1H), 7.22 (s, 1H), 7.13 (d, 2H), 6.92 (d, 1H), 6.82 (d, 2H), 6.13 (s 2H), 5.67 (m, 2H), 5.05 (m, 2H), 4.00 (m, 3H), 3.88 (m, 3H), 3.72 (m, 2H), 3.24-2.71 (m, 11H), 2.40 (t, 2H), 2.16 (m, 2H), 1.88 (m, 1H), 1.67 (m, 1H), 1.53 (m, 1H), 0.94 (m, 6H). MS(ESI): 692(M+H).

後処理

  1. waitAfter 18 hours TLC indicated
  2. customthe reaction
  3. concentrationThe solution was concentrated to dryness at reduced pressure

出典と根拠

ORDレコード
ord-6be38211d30941e687aa542eece7263e
出典データセット
uspto-grants-2013_06
特許番号
US08455497B2

反応ノート

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