Diisopropylethylamine → HCID 57955610, compound

HRID 914229Notes

Reaction equation

HRID 914229 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42]2[CH:48]=[CH:47][C:45]([NH2:46])=[CH:44][CH:43]=2)[CH2:37][CH2:36]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:46][C:45]5[CH:44]=[CH:43][C:42]([CH2:41][N:38]6[CH2:37][CH2:36][N:35]([CH3:34])[CH2:40][CH2:39]6)=[CH:48][CH:47]=5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

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 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acidHCID 67117850HCID 67117850, compound

Product 1

HCID 57955610HCID 57955610, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a dry round bottom flask, 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid (89.4 mg, 0.2 mmol), 4-((4-methylpiperazin-1-yl)methyl)aniline hydrochloride (66.7 mg, 0.24 mmol) were dissolved in dry N,N-dimethylformamide (3.0 mL). Then added diisopropylethylamine (107 μL, 0.6 mmol) and finally HATU (114 mg, 0.3 mmol) to the reaction, continued at room temperature for 2 hours. After completion, purified the product using reverse phase HPLC using water-acetonitrile solvent system. Pure fractions were mixed and evaporated to a minimal amount then basified with sat.NaHCO3 solution and extracted into EtOAc ((2×100 mL), combined organic layer was washed with sat. brine solution, dried over Na2SO4 and evaporated to get the pure product 72 mg (57% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.80 (m, 6H) 1.97 (br. s., 2H) 2.15 (s, 3H) 2.34 (br. s., 8H) 3.42 (s, 2H) 3.93 (s, 3H) 4.07 (t, J=12 Hz, 2H) 4.80 (t, J=8.21 Hz, 1H) 7.26 (d, J=8.59 Hz, 2H) 7.51-7.67 (m, 2H) 7.70 (m, J=8.59 Hz, 2H) 8.05 (s, 1H) 8.29 (s, 1H) 8.37 (d, J=8.34 Hz, 1H) 10.09 (s, 1H). [M+H] calc'd for C33H40F2N8O3, 635. found 635.

Workup

  1. customAfter completion, purified the product
  2. additionPure fractions were mixed
  3. customevaporated to a minimal amount
  4. extractionNaHCO3 solution and extracted into EtOAc ((2×100 mL)
  5. washwas washed with sat. brine solution
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-421534de7ab740ba998b768211e6f6c9
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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