Triethylamine → HCID 68153368, compound

HRID 1405415Notes

Reaction equation

HRID 1405415 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:9][CH2:8][N:7]2[C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][CH:12]=[C:6]2[C:5]21[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2.[CH:22]([O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](O)=[O:31])=[CH:28][C:27]=1[O:35][CH3:36])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C=O)C>[CH:22]([O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:19]2[CH2:20][CH2:21][C:5]3([N:4]([CH3:3])[CH2:9][CH2:8][N:7]4[C:10]([C:13]([F:14])([F:15])[F:16])=[CH:11][CH:12]=[C:6]34)[CH2:17][CH2:18]2)=[O:31])=[CH:28][C:27]=1[O:35][CH3:36])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 20639154-Isopropoxy-3-methoxybenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68153356HCID 68153356, compound

Product 1

HCID 68153368HCID 68153368, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2′-methyl-6′-(trifluoromethyl)-3′,4′-dihydro-2′H-spiro[piperidine-4,1′-pyrrolo[1,2-a]pyrazine]dihydrochloride (69 mg, 0.20 mmol), 4-isopropoxy-3-methoxybenzoic acid (42 mg, 0.20 mmol), HATU (76 mg, 0.20 mmol), Et3N (112 μL, 0.80 mmol) and DMF (2 mL) was allowed to stir at room temperature for 3 h. The mixture was filtered and purified by reverse-phase preparatory HPLC (10-99% ACN/water). The desired fractions were concentrated to give (4-isopropoxy-3-methoxyphenyl)(2′-methyl-6′-(trifluoromethyl)-3′,4′-dihydro-2′H-spiro[piperidine-4,1′-pyrrolo[1,2-a]pyrazine]-1-yl)methanone as an amorphous white solid. ESI-MS m/z calc. 465.2, found 466.3 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.01 (d, J=1.7 Hz, 1H), 6.97 (dd, J=8.2, 1.7 Hz, 1H), 6.88 (d, J=8.3 Hz, 1H), 6.53 (d, J=3.0 Hz, 1H), 5.94 (d, J=3.5 Hz, 1H), 4.57 (dt, J=12.2, 6.1 Hz, 1H), 4.52 (s, 1H), 3.99 (s, 2H), 3.87 (s, 3H), 3.69 (s, 1H), 3.40 (s, 1H), 3.34 (t, J=5.4 Hz, 3H), 2.39 (s, 3H), 2.11 (s, 2H), 1.82 (s, 2H), 1.38 (d, J=6.1 Hz, 6H).

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by reverse-phase preparatory HPLC (10-99% ACN/water)
  3. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-8e4d931a1ba44aedaf7212c13e9f05b8
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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