1,2-Dichloroethane → N-{(6S,9R)-6-(2,3-Difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl}-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 133137Notes

Reaction equation

HRID 133137 reaction equation
C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:22][C:23]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=1[C@H:30]1[CH2:36][N:35]2[C:37]([C:40]3([C:43]([F:46])([F:45])[F:44])[CH2:42][CH2:41]3)=[CH:38][N:39]=[C:34]2[C@H:33]([NH2:47])[CH2:32][CH2:31]1.[O:48]=[C:49]1[NH:57][C:52]2=[N:53][CH:54]=[CH:55][CH:56]=[C:51]2[C:50]21[CH2:65][C:64]1[C:59](=[CH:60][CH:61]=[C:62]([C:66](O)=[O:67])[CH:63]=1)[CH2:58]2>CN(C)C=O>[F:22][C:23]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=1[C@H:30]1[CH2:36][N:35]2[C:37]([C:40]3([C:43]([F:46])([F:44])[F:45])[CH2:42][CH2:41]3)=[CH:38][N:39]=[C:34]2[C@H:33]([NH:47][C:66]([C:62]2[CH:63]=[C:64]3[C:59](=[CH:60][CH:61]=2)[CH2:58][C:50]2([C:51]4[C:52](=[N:53][CH:54]=[CH:55][CH:56]=4)[NH:57][C:49]2=[O:48])[CH2:65]3)=[O:67])[CH2:32][CH2:31]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 59734934(+/-)-2'-Oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid2×HCID 67526453(6S,9R)-6-(2,3-difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine

Product 1

HCID 11685996N-{(6S,9R)-6-(2,3-Difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-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

Triethylamine (18.0 μL, 0.129 mmol), EDC (17 mg, 0.086 mmol), and HOBT (7.0 mg, 0.043 mmol) were added to a solution of (6S,9R)-6-(2,3-difluorophenyl)-3-[1-(trifluoromethyl)cyclopropyl]-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine from Step A (16 mg, 0.043 mmol) and the hydrochloride salt of (±)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (14.0 mg, 0.043 mmol, described in Intermediate 2) in N,N-dimethylformamide (1 mL). After 18 h, the reaction mixture was filtered and purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—95:5:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=634 (M+1). HRMS: m/z=634.2265; calculated m/z=634.2236 for C34H29F5N5O2.

Workup

  1. filtrationthe reaction mixture was filtered
  2. custompurified by HPLC
  3. washeluting with a gradient of H2O

Sources & evidence

ORD record
ord-22f29991f4214909a4138b8ec1d090e0
Source dataset
uspto-grants-2008_06
Patent number
US07390798B2

Reaction notes

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