1,2-Dichloroethane → N-[(7R)-4-chloro-10-(1-hydroxy-1-methylethyl)-3,6,7,12-tetrahydroimidazo[1',2':1,7]azepino[3,4-e]indazol-7-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 2400379Notes

Reaction equation

HRID 2400379 reaction equation
[NH2:1][CH:2]1[C:16]2=[N:17][CH:18]=[C:19]([C:20]([OH:23])([CH3:22])[CH3:21])[N:15]2[CH2:14][C:5]2[C:6]3[CH:7]=[N:8][NH:9][C:10]=3[C:11]([Cl:13])=[CH:12][C:4]=2[CH2:3]1.[O:24]=[C:25]1[NH:33][C:28]2=[N:29][CH:30]=[CH:31][CH:32]=[C:27]2[C:26]21[CH2:41][C:40]1[C:35](=[CH:36][CH:37]=[C:38]([C:42](O)=[O:43])[CH:39]=1)[CH2:34]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:13][C:11]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:14][N:15]3[C:19]([C:20]([OH:23])([CH3:21])[CH3:22])=[CH:18][N:17]=[C:16]3[C@H:2]([NH:1][C:42]([C:38]3[CH:39]=[C:40]4[C:35](=[CH:36][CH:37]=3)[CH2:34][C:26]3([C:27]5[C:28](=[N:29][CH:30]=[CH:31][CH:32]=5)[NH:33][C:25]3=[O:24])[CH2:41]4)=[O:43])[CH2:3][C:4]=2[CH:12]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 596266982-[7-Amino-4-chloro-3,6,7,12-tetrahydroimidazo[1',2':1,7]azepino[3,4-e]indazol-10-yl]propan-2-olHCID 59734934(+/-)-2'-Oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid

Product 1

HCID 44182403N-[(7R)-4-chloro-10-(1-hydroxy-1-methylethyl)-3,6,7,12-tetrahydroimidazo[1',2':1,7]azepino[3,4-e]indazol-7-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-[7-amino-4-chloro-3,6,7,12-tetrahydroimidazo[1′,2′:1,7]azepino[3,4-e]indazol-10-yl]propan-2-ol (100 mg, 0.3 mmole) and (±)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (78 mg, 0.28 mmol) [Bell et al. WO 2006/031606], HOBT (43 mg, 0.28 mmol), and EDC (54 mg, 0.28 mmol) in DMF (2 mL) was stirred at ambient temperature for 1 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H-90:10:0.1 to 5:95:0.1. The pure, product-containing fractions were combined and made basic with saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (2×20 mL), and the combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound as an off white solid. MS: m/z=594 (M+1)

Workup

  1. customThe reaction mixture was purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionThe resulting mixture was extracted with EtOAc (2×20 mL)
  5. washthe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d4dec474c9d940419c2523b12a05e2b5
Source dataset
uspto-grants-2014_08
Patent number
US08796260B2

Reaction notes

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