Cyclopropanemethanamine → HCID 71280490, compound

HRID 246461Notes

Reaction equation

HRID 246461 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29](O)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CN(C(ON1N=N[C:42]2[CH:43]=[CH:44][CH:45]=[N:46]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C1(CN)CC1>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29]([NH:46][CH2:45][CH:44]5[CH2:42][CH2:43]5)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280490HCID 71280490, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (0.07 g, 0.15 mmol) and HATU (0.07 g, 0.18 mmol) in DMF (4.0 mL) was added N,N-diisopropyl-ethylamine (0.024 g, 0.032 mL, 0.18 mmol). After 30 min, cyclopropylmethanamine (0.016 g, 0.23 mmol) was added. After 18 h the reaction mixture was diluted with ethyl acetate and water. The aqueous phase was extracted with EtOAc then the combined organic phase was washed with water and brine, dried (MgSO4). filtered and concentrated. The residue was purified by chromatography (silica, 24 g Analogix column, 30-100% EtOAc in hexanes, gradient over 40 min) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(cyclopropylmethyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (0.049 g, 0.096 mmol, 63%) as a white solid. 1H NMR (CDCl3) δ: 9.25 (s, 1H), 8.47 (d, J=8.8 Hz, 1H), 8.30-8.39 (m, 2H), 7.49 (s, 1H), 7.21 (d, J=8.8 Hz, 1H), 5.73 (s, 2H), 4.17 (s, 3H), 3.59 (t, J=8.2 Hz, 2H), 3.42-3.54 (m, 2H), 1.22 (dd, J=13.1, 6.5 Hz, 1H), 0.95 (t, J=8.0 Hz, 2H), 0.66 (d, J=7.5 Hz, 2H), 0.40 (d, J=4.3 Hz, 2H), −0.04 (s, 9H)

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. washthe combined organic phase was washed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (silica, 24 g Analogix column, 30-100% EtOAc in hexanes, gradient over 40 min)

Sources & evidence

ORD record
ord-78e253e710634a19aebef77230cc815b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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