2-Cyano-4-methylpent-2-enoic acid → HCID 90001185, compound

HRID 1778439Notes

Reaction equation

HRID 1778439 reaction equation
[C:1]([C:3](=[CH:7][CH:8]([CH3:10])[CH3:9])[C:4]([OH:6])=O)#[N:2].[NH:11]1[CH2:14][CH:13]([CH2:15][N:16]2[C:20]3=[N:21][CH:22]=[N:23][C:24]([NH2:25])=[C:19]3[C:18]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:28][C:27]=3[F:39])=[N:17]2)[CH2:12]1.C1CN([P+](ON2N=NC3C=CC=NC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH2:25][C:24]1[N:23]=[CH:22][N:21]=[C:20]2[N:16]([CH2:15][CH:13]3[CH2:14][N:11]([C:4]([C:3](=[CH:7][CH:8]([CH3:10])[CH3:9])[C:1]#[N:2])=[O:6])[CH2:12]3)[N:17]=[C:18]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:28][C:27]=3[F:39])[C:19]=12

Participants

5

Reactant 3

HCID 2925472-Cyano-4-methylpent-2-enoic acidHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 90001546HCID 90001546, compound

Product 1

HCID 90001185HCID 90001185, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-cyano-4-methyl-pent-2-enoic acid (48.12 mg, 0.350 mmol), 1-(azetidin-3-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine (90 mg, 0.230 mmol) in DCM (2 mL) was added PyAOP (134.9 mg, 0.250 mmol) and TEA (0.1 mL, 0.690 mmol) and the resulting yellow solution stirred at rt for 1 h. LCMS showed that the reaction was completed and the crude mixture was directly loaded onto a silica gel cartridge for purification (0.2 to 3% MeOH: CH2Cl2). Removal of solvent from cleanest fractions afforded afforded 2-[3-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carbonyl]-4-methyl-pent-2-enenitrile (12 mg LCMS. (M+1=512).

Workup

  1. customthe crude mixture was directly loaded onto a silica gel cartridge for purification (0.2 to 3% MeOH: CH2Cl2)
  2. customRemoval of solvent from cleanest fractions
  3. customafforded

Sources & evidence

ORD record
ord-6f279c966bfa4cada7696ed40f1de0cc
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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