Triethylamine → (S)-6-Amino-2-[3-((13S,16R)-13-isopropyl-15-oxo-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(21),18(22),19-trien-16-yl)ureido]hexanoic acid

HRID 1022996ノート

反応式

HRID 1022996 の反応式
[NH2:1][C@@H:2]1[CH2:21][C:20]2=[CH:22][CH:23]=[C:17]([CH:18]=[CH:19]2)[O:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C@H:5]([CH:24]([CH3:26])[CH3:25])[NH:4][C:3]1=[O:27].[C:28](N1C=CN=C1)(N1C=CN=C1)=[O:29].C(N(CC)CC)C.Cl.[NH2:48][C@@H:49]([CH2:57][CH2:58][CH2:59][CH2:60][NH:61]C(OC(C)(C)C)=O)[C:50]([O:52]C(C)(C)C)=[O:51]>CN(C=O)C>[NH2:61][CH2:60][CH2:59][CH2:58][CH2:57][C@H:49]([NH:48][C:28]([NH:1][C@@H:2]1[CH2:21][C:20]2=[CH:19][CH:18]=[C:17]([CH:23]=[CH:22]2)[O:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C@H:5]([CH:24]([CH3:25])[CH3:26])[NH:4][C:3]1=[O:27])=[O:29])[C:50]([OH:52])=[O:51]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 13819885Ne-Boc-L-lysine tert-butyl ester hydrochlorideHCID 67028556(13S,16R)-16-Amino-13-isopropyl-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(21),18(22),19-trien-15-one

生成物 1

HCID 44544518(S)-6-Amino-2-[3-((13S,16R)-13-isopropyl-15-oxo-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(21),18(22),19-trien-16-yl)ureido]hexanoic acid収率 59.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 0.18 g (0.37 mmol) of (13S,16R)-16-amino-13-isopropyl-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(21),18(22),19-trien-15-one in 3.8 ml of DMF was added to 60 mg (0.37 mmol) of 1,1′-carbonyldiimidazole and, after addition of 0.2 ml (0.15 g, 1.47 mmol) of triethylamine, stirred under argon. After 10 min, 124 mg (0.37 mmol) of tert-butyl(S)-2-amino-6-tert-butoxycarbonylaminohexanoate hydrochloride were added, and the mixture was stirred for 3 h. It was concentrated and partitioned between water and ethyl acetate, and the organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC. The required fractions were combined and concentrated. The residue was taken up in 20 ml of dichloromethane/TFA (1:1, v/v) and left to stand for 2 h. The mixture was concentrated, dissolved in 1N hydrochloric acid with a little acetonitrile and freeze dried. An amorphous solid (0.12 g) was obtained as hydrochloride.

後処理

  1. stirringthe mixture was stirred for 3 h
  2. concentrationIt was concentrated
  3. custompartitioned between water and ethyl acetate
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC
  8. concentrationconcentrated
  9. waitv/v) and left
  10. waitto stand for 2 h
  11. concentrationThe mixture was concentrated
  12. dissolutiondissolved in 1N hydrochloric acid with a little acetonitrile and freeze
  13. customdried

出典と根拠

ORDレコード
ord-00d389db133946c3b57b5dfde9aea5d6
出典データセット
uspto-grants-2014_05
特許番号
US08722655B2

反応ノート

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