Diisopropylethylamine → 5-[7-(3-Diethylamino-propionyl)-5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 450221Notes

Reaction equation

HRID 450221 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[C:23]5[CH2:31][CH2:30][NH:29][CH2:28][C:24]=5[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[CH2:68]([N:70]([CH2:76][CH3:77])[CH2:71][CH2:72][C:73](O)=[O:74])[CH3:69]>CN(C=O)C>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[C:23]5[CH2:31][CH2:30][N:29]([C:73](=[O:74])[CH2:72][CH2:71][N:70]([CH2:76][CH3:77])[CH2:68][CH3:69])[CH2:28][C:24]=5[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3084241N,N-diethyl-beta-alanine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 462242625-(5,6,7,8-Tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Product 1

HCID 593945005-[7-(3-Diethylamino-propionyl)-5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide, Example 31-C, (120 mg, 0.26 mmol), HATU (198 mg, 0.52 mmol), DIEA (0.2 mL, 1.30 mmol) and DMF (5 mL) is added 3-diethylamino-propionic acid hydrochloride (47 mg, 0.26 mmol). After stirring at rt for 2 h the contents of the flask are partitioned between DCM and 10% aqueous LiCl. Organic layer is removed, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is then separated via semi-prep HPLC (C18; 10-100% I/H2O with 0.1% NH4OH) to give the title compound. MS (ESI) m/z 581.2 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.40-8.48 (m, 1H), 8.33 (d, J=8.8 Hz, 1H), 8.06 (s, 1H), 7.94 (d, J=3.5 Hz, 1H), 7.89 (d, J=8.6 Hz, 1H), 7.57 (t, J=8.1 Hz, 1H), 7.36-7.47 (m, 2H), 7.10 (dd, J=9.0, 2.1 Hz, 1H), 6.74 (d, J=3.8 Hz, 1H), 4.71-4.79 (m, 2H), 3.85-4.05 (m, 2H), 3.20 (d, J=5.8 Hz, 2H), 2.84-3.08 (m, 8H), 1.23 (q, J=7.1 Hz, 6H).

Workup

  1. customare partitioned between DCM and 10% aqueous LiCl
  2. customOrganic layer is removed
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is then separated via semi-prep HPLC (C18; 10-100% I/H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-a7575d3cab8b42848155da0f0fbe6ef9
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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