Phosphoric Acid → HCID 121317864, compound

HRID 58190Notes

Reaction equation

HRID 58190 reaction equation
[OH:1][P:2]([OH:5])([OH:4])=[O:3].[Cl:6][C:7]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([O:15][CH3:16])=[C:9]([Cl:17])[C:8]=1[NH:18][C:19](=[O:49])[N:20]([C:22]1[N:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N:35]3[CH2:40][CH2:39][N:38]([CH:41]([CH3:43])[CH3:42])[CH2:37][CH2:36]3)=[CH:31][C:30]=2[NH:44][C:45](=[O:48])[CH:46]=[CH2:47])[CH:23]=1)[CH3:21]>C1COCC1.CO>[P:2](=[O:1])([OH:5])([OH:4])[OH:3].[Cl:17][C:9]1[C:10]([O:15][CH3:16])=[CH:11][C:12]([O:13][CH3:14])=[C:7]([Cl:6])[C:8]=1[NH:18][C:19](=[O:49])[N:20]([C:22]1[N:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N:35]3[CH2:40][CH2:39][N:38]([CH:41]([CH3:43])[CH3:42])[CH2:37][CH2:36]3)=[CH:31][C:30]=2[NH:44][C:45](=[O:48])[CH:46]=[CH2:47])[CH:23]=1)[CH3:21]

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 118026171HCID 118026171, compound

Product 1

HCID 121317864HCID 121317864, compound

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

The title compound was synthesized following the approach outlined in Procedure 2J (Example 145), substituting 4-(4-isopropylpiperazin-1-yl)-2-nitroaniline (procedure shown below) in step (b) and omitting steps (d) and (e) to afford the free base of the title compound (0.1 g, overall yield: 9.7%) as an off-white solid. MS (ESI): 643.1 [M+H]+. 85% H3PO4 was slowly added to a solution of N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-isopropylpiperazin-1-yl)phenyl)acrylamide (0.1 g) in 95% THF-MeOH (5 mL). The resulting reaction mixture was then allowed to stir at room temperature for 30 min., evaporated the solvent and triturated with diethyl ether, dried under vacuum to afford the title compound (0.16 g) as a off white solid. 1HNMR (DMSO-d6, 400 MHz): δ 12.08 (s, 1H), 9.62 (s, 1H), 8.76 (s, 1H), 8.32 (s, 1H), 7.30 (d, 2H), 6.89 (d, 1H), 6.81 (d, 1H), 6.46-6.49 (m, 1H), 6.21-6.25 (m, 2H), 5.72 (d, 1H), 3.93 (s, 6H), 3.35-3.41 (m, 1H), 3.23 (s, 3H), 3.12-3.17 (m, 4H), 2.67-2.70 (m, 41H), 1.05-1.11 (m, 6H); MS (ESI): 643.3 (M+1); HPLC: 95.41%, rt: 6.48 min.

Workup

  1. customThe resulting reaction mixture
  2. customevaporated the solvent
  3. customtriturated with diethyl ether
  4. customdried under vacuum

Sources & evidence

ORD record
ord-9c3fc43ed06d411e970d3ab5595249b9
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

Loading…