Methylamine → HCID 57656330, compound

HRID 911748Notes

Reaction equation

HRID 911748 reaction equation
F[B-](F)(F)F.[N:6]1(OC(N(C)C)=[N+](C)C)[C:10]2C=CC=CC=2N=N1.[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][C:34]2[C:37]([S:42][CH2:43][CH2:44][CH2:45][C:46]([OH:48])=O)=[C:38]([Cl:41])[CH:39]=[CH:40][C:33]=2[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].CN.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[C:23]([O:27][C:28]([N:30]1[CH2:36][CH2:35][C:34]2[C:37]([S:42][CH2:43][CH2:44][CH2:45][C:46](=[O:48])[NH:6][CH3:10])=[C:38]([Cl:41])[CH:39]=[CH:40][C:33]=2[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57656130HCID 57656130, compound

Product 1

HCID 57656330HCID 57656330, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Add O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (123 mg, 0383 mmol) portion wise to a solution of 3-tert-butoxycarbonyl-7-chloro-6-(3-carboxy-propylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (146 mg, 0365 mmol) and methylamine (182 μL, 0.365 mmol) in anhydrous DMF (5 mL) under nitrogen at 0° C. Stir for 15 min then add diisopropylethylamine (127 μL, 0.73 mmol) in anhydrous DMF (1 mL) and continue to stir at, 0° C. for 1 h. Warm to room temperature and continue to stir overnight Pour into water (50 mL) and extract with EtOAc (3×20 mL). Wash the combined organic extracts with saturated aqueous NaHCO3 (50 mL) and brine (50 mL). Dry over MgSO4, filtrate and concentrate in vacuo to give a pale yellow oil (74 mg). MS (ES+) m/z: 398 (M+H)+. Purify using Mass-guided reverse phase HPLC [Supelco Discovery C18 column (21.2×100 mm, 5 μm packing), 25 mL/min flow rate, eluting with water/acetonitrile/acetic acid gradient over 12 min, fraction collection triggered by Electrospray MS]. Concentrate in vacuo to give the desired intermediate as a colourless oil (30 mg, 20%). MS (ES+) m/z: 435 (M+Na)+.

Workup

  1. stirringto stir at, 0° C. for 1 h
  2. stirringto stir overnight
  3. extractionextract with EtOAc (3×20 mL)
  4. washWash the combined organic extracts with saturated aqueous NaHCO3 (50 mL) and brine (50 mL)
  5. dry with materialDry over MgSO4, filtrate
  6. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-45f57577cdbd4fe5a8a8fc63fd49c4b1
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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