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 1615773노트

반응식

HRID 1615773 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1f505d3eae764bf692584a4ba7f82db1
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765763B2

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