1,2-Dichloroethane → N-[(7R)-4-Chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 552569Notes

Reaction equation

HRID 552569 reaction equation
CS(O)(=O)=O.CS(O)(=O)=O.[NH2:11][C@H:12]1[C:26](=[O:27])[N:25]([CH2:28][C:29]([F:32])([F:31])[F:30])[CH2:24][C:15]2[C:16]3[CH:17]=[N:18][NH:19][C:20]=3[C:21]([Cl:23])=[CH:22][C:14]=2[CH2:13]1.[O:33]=[C:34]1[NH:42][C:37]2=[N:38][CH:39]=[CH:40][CH:41]=[C:36]2[C:35]21[CH2:50][C:49]1[C:44](=[CH:45][CH:46]=[C:47]([C:51](O)=[O:52])[CH:48]=1)[CH2:43]2.C(N(CC)C(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Cl:23][C:21]1[C:20]2[NH:19][N:18]=[CH:17][C:16]=2[C:15]2[CH2:24][N:25]([CH2:28][C:29]([F:31])([F:30])[F:32])[C:26](=[O:27])[C@H:12]([NH:11][C:51]([C:47]3[CH:48]=[C:49]4[C:44](=[CH:45][CH:46]=3)[CH2:43][C:35]3([C:36]5[C:37](=[N:38][CH:39]=[CH:40][CH:41]=5)[NH:42][C:34]3=[O:33])[CH2:50]4)=[O:52])[CH2:13][C:14]=2[CH:22]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59734934(+/-)-2'-Oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acidHCID 86640003(7R)-7-Amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one bis-methanesulfonate

Product 1

HCID 24987420N-[(7R)-4-Chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[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 mixture of (7R)-7-amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one bis-methanesulfonate from Step B (20 mg, 0.038 mmol), (±)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (11 mg, 0.038 mmol) [Bell et al. WO 2006/031606], N,N-diisopropylethylamine (25 mg, 33 uL, 0.19 mmol), HOBT (7.0 mg, 0.046 mmol), and EDC (8.8 mg, 0.046 mmol) in DMF (0.5 mL) was stirred at ambient temperature for 2 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 concentrated in vacuo to provide the title compound. MS: m/z=595.

Workup

  1. customThe reaction mixture was purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-6612219bb2574937acae6fbed065f76f
Source dataset
uspto-grants-2011_05
Patent number
US07951795B2

Reaction notes

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