Triethylamine → (S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione

HRID 2379001Notes

Reaction equation

HRID 2379001 reaction equation
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:4]=2[CH:3]=1.[NH:26]1[C:30]2([CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[C:29](=[O:36])[NH:28][C:27]1=[O:37].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:21][C:22]([F:24])([F:23])[F:25])[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([N:33]3[CH2:32][CH2:31][C:30]4([NH:26][C:27](=[O:37])[NH:28][C:29]4=[O:36])[CH2:35][CH2:34]3)=[O:19])[CH2:15][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1209891,3,8-Triazaspiro[4.5]decane-2,4-dioneHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59732027(S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid

Product 1

HCID 23658011(S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dioneYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (50 mg, 0.133 mmol) in DMF (2.0 mL) were added 1,3,8-triazaspiro[4.5]decane-2,4-dione (34 mg, 0.2 mmol) followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (47 mg, 0.15 mmol) and triethylamine (1.0 mL). After 2 h, the solvent was removed under reduced pressure and the crude product was purified by PrepHPLC to give (S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione (32 mg) in 46% yield. MS (ESI) 527 (M+H); Rf=1.66.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customthe crude product was purified by PrepHPLC

Sources & evidence

ORD record
ord-74fdc4e809fb46eea71f96d342cd486d
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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