Cesium carbonate → tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 626819Notes

Reaction equation

HRID 626819 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:38](Cl)[CH3:39])[C:22]2[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][C:23]=2[C:36]=1[CH3:37]>CN(C)C=O.C(OCC)(=O)C>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:38]([C:21]3[C:22]4[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:24][C:23]=4[C:36]([CH3:37])=[C:19]([Cl:18])[CH:20]=3)[CH3:39])[N:9]=[C:8]([CH3:7])[C:16]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 86697516tert-Butyl 7-chloro-9-(1-chloroethyl)-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateHCID 178434474HCID 178434474, compound

Product 1

HCID 71765363tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (500 mg, 2 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (150 mg, 0.98 mmol) in N,N-dimethylformamide (30 mL) and stirred for 10 minutes. To this was added tert-butyl 7-chloro-9-(1-chloroethyl)-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (290 mg, 0.82 mmol) in N,N-dimethylformamide (1 mL) and the reaction was stirred at 80° C. for 1 hour. The mixture was diluted with ethyl acetate and washed with water and brine. The extracts were dried over sodium sulfate, filtered and evaporated. The crude was dissolved in methylene chloride and filtered to remove insoluble material (unwanted regioisomer). Purification on silica gel using ethyl acetate in hexanes (0-100%) followed by methanol in ethyl acetate (0-15%) gave the desired compound (240 mg, 62%). LCMS calculated for C23H30ClN6O3(M+H)+: m/z=473.2; found: 473.2. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.29 (m, 1 H), 6.32 (m, 1 H), 4.70 (m, 1 H), 4.40 (m, 1 H), 3.83 (m, 2 H), 3.57 (m, 2 H), 2.58 (s, 3 H), 2.48 (m, 3 H), 1.78 (m, 3 H), 1.39 (, 9H).

Workup

  1. stirringthe reaction was stirred at 80° C. for 1 hour
  2. washwashed with water and brine
  3. dry with materialThe extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe crude was dissolved in methylene chloride
  7. filtrationfiltered
  8. customto remove insoluble material (unwanted regioisomer)
  9. customPurification on silica gel

Sources & evidence

ORD record
ord-1ee163424a8744b899a2713f3180e47d
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

Loading…