Dichloromethane → HCID 71765551, compound

HRID 626829Notes

Reaction equation

HRID 626829 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:24]4[O:23][CH2:22][C@H:21]([CH3:25])[N:20](C(OC(C)(C)C)=O)[CH2:19][C:18]=4[C:17]([F:33])=[C:16]([Cl:34])[CH:15]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.C(Cl)Cl.C(N(CC)C(C)C)(C)C.[CH3:47][S:48](Cl)(=[O:50])=[O:49]>>[Cl:34][C:16]1[CH:15]=[C:14]([CH:12]([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]3[C:10]([CH3:11])=[N:9]2)[CH3:13])[C:24]2[O:23][CH2:22][C@H:21]([CH3:25])[N:20]([S:48]([CH3:47])(=[O:50])=[O:49])[CH2:19][C:18]=2[C:17]=1[F:33]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86697522HCID 86697522, compound

Product 1

HCID 71765551HCID 71765551, compound

Conditions

Temperature
0 °C

Procedure

tert-Butyl (3S)-9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-fluoro-3-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (13 mg, 0.026 mmol) was stirred in methylene chloride (100 μL, 2 mmol) with N,N-diisopropylethylamine (14 μL, 0.079 mmol) and cooled to 0° C. Methanesulfonyl chloride (2.6 μL, 0.034 mmol) was added, and the mixture was stirred at 0° C. for 1 hr. The mixture was evaporated and diluted with methanol. The reactions were purified by prep HPLC on C-18 column eluting water:acetonitrile gradient buffered pH 10 to give two enantiomers: Peak #1 (Example 35): LCMS calculated for C19H23ClFN6O3S (M+H)+: m/z=469.1; found: 469.1; Peak #2 (Example 36): LCMS calculated for C19H23ClFN6O3S (M+H)+: m/z=469.1; found: 469.1.

Workup

  1. customThe mixture was evaporated
  2. additiondiluted with methanol
  3. customThe reactions were purified by prep HPLC on C-18 column
  4. washeluting water
  5. customacetonitrile gradient buffered pH 10 to give two enantiomers

Sources & evidence

ORD record
ord-f9381b06773a40bcaf13f2a69e3e59d8
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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