Diisopropylethylamine → (3S,9aS)-tert-butyl 8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate

HRID 1502180Notes

Reaction equation

HRID 1502180 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]([CH2:39][C:40](O)=[O:41])=[CH:35][N: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:34]=[CH:35][C:36]([CH2:39][C:40]([N:18]3[CH2:17][CH2:16][N:14]4[CH2:15][C@H:10]([C:5]5[CH:6]=[CH:7][C:8]([F:9])=[C:3]([C:1]#[N:2])[C:4]=5[CH3:27])[N:11]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:12][C@@H:13]4[CH2:19]3)=[O:41])=[CH:37][N:38]=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 71271513(3S,9aS)-tert-butyl 3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylateHCID 89619099[2-(1H-tetrazol-1-yl)pyrimidin-5-yl]acetic acid

Product 1

HCID 89619169(3S,9aS)-tert-butyl 8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetyl)-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 (3S,9aS)-tert-butyl 3-(3-cyano-4-fluoro-2-methylphenyl)hexahydro-1H-pyrazino[1,2-a]pyrazine-2(6H)-carboxylate (46 mg, 0.123 mmol) and 2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)acetic acid (30.4 mg, 0.147 mmol) in DMF (2 mL) was added HATU (70.1 mg, 0.184 mmol) and diisopropylethylamine (64.4 μl, 0.369 mmol) and the resulting solution was stirred at rt for 1 h. Ethyl acetate (50 mL) was added and the organic phase was washed with brine (3×50 mL), dried over sodium sulphate, concentrated and the residue was purified on TLC using 10% methanol/methylene chloride to give title compound, LC/MS: [(M+23)]+=585.23; [(M+1-100-28)]+=435.20.

Workup

  1. washthe organic phase was washed with brine (3×50 mL)
  2. dry with materialdried over sodium sulphate
  3. concentrationconcentrated
  4. customthe residue was purified on TLC

Sources & evidence

ORD record
ord-16545ed74809423796f6c1dd04556f38
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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