4-cyano-1H-pyrrole-2-carboxylic acid → 4-[4-[(4-Cyano-1H-pyrrole-2-carbonyl)-amino]-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 646921Notes

Reaction equation

HRID 646921 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:8]([OH:10])=O)[NH:6][CH:7]=1)#[N:2].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[C:26]([N:31]3[CH2:36][CH2:35][CH:34]([CH3:37])[CH2:33][CH2:32]3)[CH:25]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([NH:30][C:8]([C:5]3[NH:6][CH:7]=[C:3]([C:1]#[N:2])[CH:4]=3)=[O:10])=[C:26]([N:31]3[CH2:36][CH2:35][CH:34]([CH3:37])[CH2:33][CH2:32]3)[CH:25]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

3

Reactant 2

HCID 118048114-cyano-1H-pyrrole-2-carboxylic acidHCID 686827664-[4-Amino-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 586385224-[4-[(4-Cyano-1H-pyrrole-2-carbonyl)-amino]-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

Procedure

Prepared according to the procedure from Example 53 using 4-cyano-1H-pyrrole-2-carboxylic acid (as prepared in Example 2) and 4-[4-amino-3-(4-methyl-piperidin-1-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester as prepared in Example 15, step (c). Purification of the resulting residue by silica gel preparative TLC eluting with 20% ethyl acetate in dichloromethane afforded the title compound in 47% as an off-white solid. 1H-NMR (400 MHz, CDCl3): δ 11.13 (br s, 1H), 9.05 (s, 1H), 8.29 (d, 1H, J=8.9), 7.48 (dd, 1H, J=3.0, 1.3 Hz), 6.88 (s, 1H), 6.84 (d, 1H, J=2.6 Hz), 6.76 (dd, 1H, J=8.9, 2.2 Hz), 3.62 (m, 4H), 3.13 (m, 4H), 3.01-2.98 (m, 2H), 2.73 (m, 2H), 1.88-1.85 (m, 2H), 1.61-1.56 (m, 2H), 1.51 (s, 9H), 1.50-1.37 (m, 2H), 1.10 (d, 3H, J=6.5 Hz). LC-MS (ESI, m/z): Calcd. for C27H37N6O3, 493.3 (M+H); found: 493.1.

Workup

  1. customPrepared
  2. customas prepared in Example 15, step (c)
  3. customPurification of the resulting residue by silica gel preparative TLC
  4. washeluting with 20% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-b693dce1b4144171adeb969ab92b4eef
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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