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

HRID 1615773ノート

反応式

HRID 1615773 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 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-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 681546322-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-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 together with 67.9 mg (0.27 mmol) (R)-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, overnight at RT. The solvent was spun off and the residue was stirred with 15 ml of a methanolic hydrochloric acid (1.25N) for 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-1f505d3eae764bf692584a4ba7f82db1
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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