Acetic Anhydride → 4-(1-acetylazetidin-3-yl)-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

HRID 626846Notes

Reaction equation

HRID 626846 reaction equation
Cl.Cl.Cl.[NH2:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([CH:15]([C:17]3[CH:18]=[C:19]([Cl:34])[C:20]([C:32]#[N:33])=[C:21]4[C:27]=3[O:26][CH2:25][CH2:24][N:23]([CH:28]3[CH2:31][NH:30][CH2:29]3)[CH2:22]4)[CH3:16])[N:12]=[C:13]([CH3:14])[C:6]=12.C(N(CC)C(C)C)(C)C.[C:44](OC(=O)C)(=[O:46])[CH3:45]>CN(C)C=O>[C:44]([N:30]1[CH2:31][CH:28]([N:23]2[CH2:22][C:21]3=[C:20]([C:32]#[N:33])[C:19]([Cl:34])=[CH:18][C:17]([CH:15]([N:11]4[C:7]5=[N:8][CH:9]=[N:10][C:5]([NH2:4])=[C:6]5[C:13]([CH3:14])=[N:12]4)[CH3:16])=[C:27]3[O:26][CH2:25][CH2:24]2)[CH2:29]1)(=[O:46])[CH3:45]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 86697539HCID 86697539, compound

Product 1

HCID 717655904-(1-acetylazetidin-3-yl)-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-carbonitrileYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The crude 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-4-azetidin-3-yl-7-chloro-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile trishydrochloride (0.015 g, 0.0278 mmol) was dissolved in N,N-dimethylformamide (2 mL) and cooled in an ice bath, and then N,N-diisopropylethylamine (0.0142 g, 0.112 mmol) and acetic anhydride (0.0032 mL, 0.033 mmol) were added. After stirring for 1 h, the product was purified without work up, by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give 4-(1-acetylazetidin-3-yl)-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 as a white amorphous solid (0.004 g, 33%). LCMS calculated for C23H26ClN8O2 (M+H)+: m/z=481.2; found: 481.2.

Workup

  1. temperaturecooled in an ice bath
  2. customthe product was purified without work up
  3. washby prep HPLC on a C-18 column eluting water

Sources & evidence

ORD record
ord-4af7a6750cb14a34baf3d8729fed6d3a
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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