Dimethylformamide → HCID 71765633, compound

HRID 626852Notes

Reaction equation

HRID 626852 reaction equation
[O:1]1[CH2:3][CH2:2]1.Cl.Cl.[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]2[N:13]([CH:17]([C:19]3[CH:20]=[C:21]([Cl:33])[C:22]([C:31]#[N:32])=[C:23]4[C:29]=3[O:28][CH:27](C)[CH2:26]NC4)[CH3:18])[N:14]=[C:15]([CH3:16])[C:8]=12.[CH2:34](N(CC)CC)C.[CH3:41][N:42]([CH3:45])[CH:43]=O>>[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]2[N:13]([CH:17]([C:19]3[CH:20]=[C:21]([Cl:33])[C:22]([C:31]#[N:32])=[C:23]4[C:29]=3[O:28][CH:27]([CH3:26])[CH2:43][N:42]([CH2:45][C:3]([OH:1])([CH3:2])[CH3:34])[CH2:41]4)[CH3:18])[N:14]=[C:15]([CH3:16])[C:8]=12

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6354Ethylene OxideHCID 8471TriethylamineHCID 86697543HCID 86697543, compound

Product 1

HCID 71765633HCID 71765633, compound

Conditions

Temperature
80 °C

Procedure

Oxirane, 2,2-dimethyl-(5.5 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-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepine-6-carbonitrile bishydrochloride (16 mg, 0.039 mmol) and triethylamine (10 μL, 0.09 mmol) in N,N-dimethylformamide (2 mL). The reaction was heated at 80° C. for 3 hrs and was allowed to cool to room temperature. The reaction was purified without workup by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two diastereomers: Peak #1 (Example 65): LCMS calculated for C23H29ClN7O2 (M+H)+: m/z=470.2; found: 470.2; Peak #2 (Example 66): LCMS calculated for C23H29ClN7O2 (M+H)+: m/z=470.2; found: 470.2.

Workup

  1. temperatureto cool to room temperature
  2. customThe reaction was purified without workup by prep HPLC on C-18 column
  3. washeluting water
  4. customacetonitrile gradient buffered pH 10 to give two diastereomers

Sources & evidence

ORD record
ord-4d99807be3a34362b0c246ce0a63f83a
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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