Ammonia → 5-{2-[7-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-3,4-dihydroisoquinolin-2(1H)-yl]-2-oxoethyl}nicotinonitrile

HRID 449463Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([N:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][C:15]([C:21]4[CH:26]=[C:25]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)[N:24]=[C:23]([NH2:34])[N:22]=4)=[CH:16][CH:17]=3)[CH2:12]2)=[O:10])[CH:5]=[N:6][CH:7]=1.[CH3:35][N:36]1CCCC1=O.N>[C-]#N.[Zn+2].[C-]#N.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.[Zn]>[NH2:34][C:23]1[N:22]=[C:21]([C:15]2[CH:14]=[C:13]3[C:18]([CH2:19][CH2:20][N:11]([C:9](=[O:10])[CH2:8][C:4]4[CH:5]=[N:6][CH:7]=[C:2]([CH:3]=4)[C:35]#[N:36])[CH2:12]3)=[CH:17][CH:16]=2)[CH:26]=[C:25]([N:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)[N:24]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A degassed mixture of 4-{2-[(5-bromopyridin-3-yl)acetyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (20 mg, 0.04 mmol), zinc cyanide (7 mg, 0.06 mmol), bis(tri-t-butylphosphine)palladium (1 mg, 0.002 mmol) and zinc (0.4 mg, 0.006 mmol) powder in anhydrous N-methylpyrrolidinone (0.1 mL, 1 mmol) was heated at 135° C. for 18 h. The mixture was adjusted to pH=10 with aqueous NH3, filtered, washed with MeOH, and purified by RP-LCMS (pH=10) to afford the desire product. Analytic LCMS (M+H)+: m/z=469.1.

Workup

filtrationfiltered
washwashed with MeOH
custompurified by RP-LCMS (pH=10)
customto afford the desire product

Sources & evidence

ORD record: ord-11ba0b510713488cafb490a415d4b64e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481732B2

Reaction notes

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