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

HRID 1429742Notes

Reaction equation

HRID 1429742 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 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

Sources & evidence

ORD record
ord-1c2ac6fe0702457690add9bf71ccb6b7
Source dataset
uspto-grants-2015_01
Patent number
US08940744B2

Reaction notes

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