Diisopropylethylamine → (3R,9aS)-tert-butyl 8-(3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-7-carbonyl)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

HRID 2175932Notes

Reaction equation

HRID 2175932 reaction equation
[C:1]([C:3]1[C:4]([CH3:27])=[C:5]([C@@H:10]2[CH2:15][N:14]3[CH2:16][CH2:17][NH:18][CH2:19][C@H:13]3[CH2:12][N:11]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].[N:28]1([C:33]2[N:38]=[CH:37][C:36]3[CH:39]([C:42](O)=[O:43])[CH2:40][CH2:41][C:35]=3[CH:34]=2)[CH:32]=[N:31][N:30]=[N:29]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[N:28]1([C:33]2[N:38]=[CH:37][C:36]3[CH:39]([C:42]([N:18]4[CH2:17][CH2:16][N:14]5[CH2:15][C@@H:10]([C:5]6[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:1]#[N:2])[C:4]=6[CH3:27])[N:11]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:12][C@@H:13]5[CH2:19]4)=[O:43])[CH2:40][CH2:41][C:35]=3[CH:34]=2)[CH:32]=[N:31][N:30]=[N:29]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 675172303-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-7-carboxylic acidHCID 86727053(3R,9aS)-tert-butyl 3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

Product 1

HCID 86727115(3R,9aS)-tert-butyl 8-(3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-7-carbonyl)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3R,9aS)-tert-butyl 3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate [I-18A](250 mg, 0.668 mmol) and 3-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[c]pyridine-7-carboxylic acid [I-65] (201 mg, 0.868 mmol) in DMF (4 mL) was added HATU (381 mg, 1.00 mmol) followed by addition of diisopropylethylamine (350 μL, 2.00 mmol). The resulting solution was stirred at rt for 1 h. Ethyl acetate (100 mL) was added and the mixture was washed with saturated sodium bicarbonate (3×100 mL), dried over sodium sulphate, concentrated and the residue was purified by preparative TLC eluting with 10% methanol/methylene chloride to give the title compound. LC/MS: (M+1)+: 588.2.

Workup

  1. washthe mixture was washed with saturated sodium bicarbonate (3×100 mL)
  2. dry with materialdried over sodium sulphate
  3. concentrationconcentrated
  4. customthe residue was purified by preparative TLC
  5. washeluting with 10% methanol/methylene chloride

Sources & evidence

ORD record
ord-d0d1b80575d64b069446964f3dda6fbe
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Reaction notes

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