Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 178520839, compound

HRID 1910110Notes

Reaction equation

HRID 1910110 reaction equation
Cl.O1CCOCC1.[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([C:27](O)=[O:28])=[CH:26][C:20]=3[N:19]=2)[N:9]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:54][CH:55]([CH:65]1[CH2:67][CH2:66]1)[CH2:56][C:57]([NH:59][C:60]1[NH:61][CH:62]=[CH:63][N:64]=1)=[O:58]>C(Cl)Cl>[CH:65]1([CH:55]([NH:54][C:27]([C:25]2[CH:24]=[CH:23][C:21]3[NH:22][C:18]([C:10]4[N:9]=[CH:8][C:17]5[C:12]([CH:11]=4)=[CH:13][CH:14]=[CH:15][CH:16]=5)=[N:19][C:20]=3[CH:26]=2)=[O:28])[CH2:56][C:57](=[O:58])[NH:59][C:60]2[NH:61][CH:62]=[CH:63][N:64]=2)[CH2:67][CH2:66]1

Participants

6

Reactant 4

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 204431481,4-Dioxane hydrochlorideHCID 66940190HCID 66940190, compoundHCID 178524149HCID 178524149, compound

Product 1

HCID 178520839HCID 178520839, compoundYield 4.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

203 mg (1.0 mmol) of 3-tert-butoxycarbonylamino-3-cyclopropyl-propionic acid (0.23 g, 1 mmol) was reacted with 380 mg (1.0 mmol) of HBTU and 130 mg (1.0 mmol) of 2-aminoimidazole sulfate as described in general procedure A. The desired amide product was isolated by column chromatography (EtOAc/silica) and carried on directly to the next step. The BOC compound in DCM (3 mL) was treated with 4.0 M HCl/dioxane (15 mL) for approximately 1 h. The solid 3-Amino-3-cyclopropyl-N-(1H-imidazol-2-yl)-propionamide (180 mg, 100%) was collected by filtration and used directly in the next step 289 mg (1 mmol) of 2-isoquinolin-3-yl-1H-benzoimidazole-5-carboxylic acid (289 mg, 1 mmol) was reacted with 380 mg (1 mmol) of HBTU and 3-amino-3-cyclopropyl-N-(1H-imidazol-2-yl)-propionamide (230 mg, 1 mmol) as described in general procedure A. A solid precipitated from the solution and was collected by filtration, washed with 1H2O and Et2O, to give 2-isoquinolin-3-yl-1H-benzoimidazole-5-carboxylic acid [1-cyclopropyl-2-(1H-imidazol-2-ylcarbamoyl)-ethyl]-amide (20 mg, 4%). LCMS: 466 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ 9.20 (s, 1H), 8.56 (s, 1H), 8.09-7.34 (m, 9H), 6.39 (s, 2H), 3.71 (t, 1H), 2.44 (m, 2H), 0.81 (m, 1H), 0.10 (m, 4H) ppm.

Workup

  1. filtrationThe solid 3-Amino-3-cyclopropyl-N-(1H-imidazol-2-yl)-propionamide (180 mg, 100%) was collected by filtration
  2. customA solid precipitated from the solution
  3. filtrationwas collected by filtration
  4. washwashed with 1H2O and Et2O

Sources & evidence

ORD record
ord-076594aa71fc47d08681dab66456e3b7
Source dataset
uspto-grants-2013_12
Patent number
US08598353B2

Reaction notes

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