4-Amino-1-Boc-piperidine → HCID 57955556, compound

HRID 1880964Notes

Reaction equation

HRID 1880964 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[C:30]([O:31][CH3:32])=[CH:29][C:25]([C:26]([OH:28])=O)=[C:24]([F:33])[CH:23]=4)=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43]C(C)(C)C)=O)[CH2:37][CH2:36]1>C(OCC)(=O)C>[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[C:30]([O:31][CH3:32])=[CH:29][C:25]([C:26]([NH:34][CH:35]5[CH2:36][CH2:37][N:38]([C:41](=[O:43])[CH2:1][N:6]([CH3:12])[CH3:7])[CH2:39][CH2:40]5)=[O:28])=[C:24]([F:33])[CH:23]=4)=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 12682914-Amino-1-Boc-piperidineHCID 252536794-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxybenzoic acid

Product 1

HCID 57955556HCID 57955556, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Using the general procedure for amide bond synthesis, 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-2-fluoro-5-methoxybenzoic acid was first reacted with tert-butyl 4-aminopiperidine-1-carboxylate. The product was diluted to ethyl acetate, washed by sodium bicarbonate aqueous solution and brine. Organic extract was dried and concentrated to a residue. It was then dissolved in a mixture of TFA and MeOH (1:1) and stirred for 1 h. After which, it was concentrated in vacuo, separated between ethyl acetate and sodium bicarbonate aqueous solution. Organic extract dried and concentrated to a residue, which was subjected to amide bond synthesis with 2-(dimethylamino)acetic acid. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (m, 2 H) 1.61 (m, 4 H) 1.73 (br. s., 4 H) 1.99 (s, 3 H) 2.19 (s, 6 H) 2.73 (m, 1 H) 3.14 (m, 3 H) 3.80-3.95 (m, 3 H) 3.95-4.20 (m, 4 H) 4.26 (m., 1 H) 4.81 (d, J=8.1 Hz, 1 H) 7.19 (d, J=6.8 Hz, 1 H) 7.92-8.10 (m, 2 H) 8.18-8.35 (m, 2 H). [M+H] calc'd for C30H39F3N8O4, 633; found 633.

Workup

  1. washwashed by sodium bicarbonate aqueous solution and brine
  2. extractionOrganic extract
  3. customwas dried
  4. concentrationconcentrated to a residue
  5. dissolutionIt was then dissolved in a mixture of TFA and MeOH (1:1)
  6. concentrationAfter which, it was concentrated in vacuo
  7. customseparated between ethyl acetate and sodium bicarbonate aqueous solution
  8. extractionOrganic extract
  9. customdried
  10. concentrationconcentrated to a residue, which
  11. customwas subjected to amide bond synthesis with 2-(dimethylamino)acetic acid
  12. customThe final compound was purified by reverse phase HPLC
  13. customto give the free base

Sources & evidence

ORD record
ord-080efcce845c44b2ac8f8a48442eeb44
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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