Dimethylcarbamoyl Chloride → HCID 59612556, compound

HRID 472637Notes

Reaction equation

HRID 472637 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH2:30][CH:31]([F:33])[F:32])=[C:6]([C:8]2[C:9]3[N:10]([N:14]=[C:15]([NH:17][C:18]4[CH:28]=[CH:27][C:21]5[CH2:22][CH2:23][NH:24][CH2:25][CH2:26][C:20]=5[CH:19]=4)[N:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH:7]=1.C(N(CC)CC)C.[CH3:41][N:42]([CH3:46])[C:43](Cl)=[O:44]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:41][N:42]([CH3:46])[C:43]([N:24]1[CH2:23][CH2:22][C:21]2[CH:27]=[CH:28][C:18]([NH:17][C:15]3[N:16]=[C:9]4[C:8]([C:6]5[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=5[O:29][CH2:30][CH:31]([F:33])[F:32])=[CH:13][CH:12]=[CH:11][N:10]4[N:14]=3)=[CH:19][C:20]=2[CH2:26][CH2:25]1)=[O:44]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 59612565HCID 59612565, compound

Product 1

HCID 59612556HCID 59612556, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To {8-[5-chloro-(2,2-difluoro-ethoxy)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl}-(2,3,4,5-tetrahydro-1H-3-benzazepin-7yl)-amine (0.054 g, 0.110 mmol) in dichloromethane (4 mL) under an atmosphere of nitrogen was added triethylamine (0.0349 g, 0.345 mmol), N,N-dimethylcarbamoyl chloride (0.0159 mL, 0.172 mmol), followed by 4-dimethylaminopyridine (0.0014 g, 0.012 mmol) and was stirred at r.t. for 3 h and concentrated. The reaction was partitioned between dichloromethane/water, washed with brine, dried over sodium sulfate, and concentrated. The product was purified using Prep TLC plates (5% methanol in dichloromethane) and concentrated to give 7-{8-[5-chloro-2-(2,2-difluoro-ethoxy)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino}-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid dimethylamide (0.030 g, 48%). MP=98-99° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.58 (s, 1H), 8.78 (d, 1H), 7.80 (s, 1H), 7.65 (d, 1H), 7.48 (m, 3H), 7.30 (d, 1H), 7.05 (m, 2H), 6.25 (br m, 1H), 4.38 (m, 2H), 3.28 (m, 4H), 2.84 (m, 4H), 2.74 (s, 6H). MS=541 (MH)+.

Workup

  1. concentrationconcentrated
  2. customThe reaction was partitioned between dichloromethane/water
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe product was purified
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3a58848f4d2b492c81ee90d9232e38fe
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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