Triethylamine → 9-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-4-(2-hydroxyethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile

HRID 626850Notes

Reaction equation

HRID 626850 reaction equation
Br[CH2:2][CH2:3][OH:4].Cl.Cl.[NH2:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]2[N:14]([CH:18]([C:20]3[CH:21]=[C:22]([Cl:33])[C:23]([C:31]#[N:32])=[C:24]4[C:30]=3[O:29][CH2:28][CH2:27][NH:26][CH2:25]4)[CH3:19])[N:15]=[C:16]([CH3:17])[C:9]=12.C(N(CC)CC)C>CN(C)C=O>[NH2:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]2[N:14]([CH:18]([C:20]3[CH:21]=[C:22]([Cl:33])[C:23]([C:31]#[N:32])=[C:24]4[C:30]=3[O:29][CH2:28][CH2:27][N:26]([CH2:2][CH2:3][OH:4])[CH2:25]4)[CH3:19])[N:15]=[C:16]([CH3:17])[C:9]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 866975369-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride

Product 1

HCID 717656309-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-4-(2-hydroxyethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrileYield 479.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromoethanol (4.7 μL, 0.066 mmol) was added to a mixture of 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride (15 mg, 0.039 mmol) (from Example 46, step 13) and triethylamine (10 μL, 0.09 mmol) in N,N-dimethylformamide (2 mL). The reaction was heated at 80° C. for 3 h and then allowed to cool. The product was purified without workup by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the desired compound as white amorphous solid (0.08 g, 50%). LCMS calculated for C20H23ClN7O2 (M+H)+: m/z=428.1; found: 428.2.

Workup

  1. temperatureto cool
  2. customThe product was purified without workup by prep HPLC on a C-18 column
  3. washeluting water

Sources & evidence

ORD record
ord-cb79681245b5494fb780648625305ab0
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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