Hydrochloric Acid → 2-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((S)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

HRID 1615774ノート

反応式

HRID 1615774 の反応式
[C:1]([CH2:4][N:5]1[C:10](=[O:11])[C:9]2([CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12]2)[N:8](C(OC(C)(C)C)=O)[CH2:7][C@H:6]1[C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[CH:26]=1)(O)=[O:2].[NH2:33][C:34]1[CH:35]=[C:36]2[C:49](=[CH:50][CH:51]=1)[CH2:48][C@@:38]1([C:46]3[C:41](=[N:42][CH:43]=[CH:44][CH:45]=3)[NH:40][C:39]1=[O:47])[CH2:37]2.Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C>[F:31][C:29]1[CH:30]=[C:25]([C@H:6]2[N:5]([CH2:4][C:1]([NH:33][C:34]3[CH:35]=[C:36]4[C:49](=[CH:50][CH:51]=3)[CH2:48][C@@:38]3([C:46]5[C:41](=[N:42][CH:43]=[CH:44][CH:45]=5)[NH:40][C:39]3=[O:47])[CH2:37]4)=[O:2])[C:10](=[O:11])[C:9]3([CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12]3)[NH:8][CH2:7]2)[CH:26]=[C:27]([F:32])[CH:28]=1

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54776259(S)-5-amino-1,3-dihydrospiro[indene-2,3-pyrrolo[2,3-b]pyridin]-2(1H)-oneHCID 68154191tert-butyl (R)-4-carboxymethyl-3-(3,5-difluoro-phenyl)-5-oxo-8,11-dioxa-1,4-diaza-spiro[5.6]dodecane-1-carboxylate

生成物 1

HCID 498420252-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((S)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

0.114 g (0.25 mmol) tert-butyl (R)-4-carboxymethyl-3-(3,5-difluoro-phenyl)-5-oxo-8,11-dioxa-1,4-diaza-spiro[5.6]dodecane-1-carboxylate were stirred overnight at RT with 67.9 mg (0.27 mmol) (S)-5-amino-1,3-dihydrospiro[inden-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, 63.3 mg (0.33 mmol) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 44.6 mg (0.33 mmol) HOBT, 35 μl (0.25 mmol) TEA and 1.5 ml DMF. The solvent was spun off and the residue was stirred with 15 ml of a methanolic hydrochloric acid (1.25N) 1 h at 50° C. The reaction mixture was concentrated by rotary evaporation and the residue was purified by PR-HPLC. The product-containing fractions were concentrated by rotary evaporation and the residue was triturated with diisopropylether. After suction filtering the solid was washed with diisopropylether and dried.

後処理

  1. concentrationThe reaction mixture was concentrated by rotary evaporation
  2. customthe residue was purified by PR-HPLC
  3. concentrationThe product-containing fractions were concentrated by rotary evaporation
  4. customthe residue was triturated with diisopropylether
  5. filtrationAfter suction filtering the solid
  6. washwas washed with diisopropylether
  7. customdried

出典と根拠

ORDレコード
ord-bcf785bb42df4d11aa5407eac84b041c
出典データセット
uspto-grants-2014_07
特許番号
US08765763B2

反応ノート

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