Trifluoroacetic acid → 2-[1-(4-benzyl-morpholin-2-ylmethyl)-5-difluoromethoxy-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246505Notes

Reaction equation

HRID 246505 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH:25]([F:27])[F:26])=[CH:21][CH:22]=3)[C:17]([C:28]3[N:29]=[C:30]4[C:36]([C:37]([NH:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:35][N:34](COCC[Si](C)(C)C)[C:31]4=[N:32][CH:33]=3)=[N:16]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[C:40]([NH:39][C:37]([C:36]1[C:30]2[C:31](=[N:32][CH:33]=[C:28]([C:17]3[C:18]4[C:23](=[CH:22][CH:21]=[C:20]([O:24][CH:25]([F:27])[F:26])[CH:19]=4)[N:15]([CH2:14][CH:10]4[O:11][CH2:12][CH2:13][N:8]([CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH2:9]4)[N:16]=3)[N:29]=2)[NH:34][CH:35]=1)=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712796062-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712800882-[1-(4-benzyl-morpholin-2-ylmethyl)-5-difluoromethoxy-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(1-((4-benzylmorpholin-2-yl)methyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (40 mg, 55.6 μmol) in dichloromethane (10 mL) was added trifluoroacetic acid (1 mL). After 15 h, the mixture was concentrated in vacuo then 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane added. After 1 h the mixture was concentrate. Purification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-[1-(4-benzyl-morpholin-2-ylmethyl)-5-difluoromethoxy-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (25 mg, 76%). MS (M+H)+=590; 1H NMR (DMSO-d6) δ: 9.04 (s, 1H), 8.39 (s, 1H), 8.18 (d, J=2.3 Hz, 1H), 7.88 (d, J=4.0 Hz, 1H), 7.36-7.41 (m, 1H), 7.29-7.33 (m, 5H), 7.22-7.27 (m, 1H), 6.98-7.21 (m, 1H), 4.54-4.68 (m, 2H), 3.96-4.03 (m, 1H), 3.74 (d, J=11.0 Hz, 1H), 3.49 (s, 2H), 3.40-3.48 (m, 1H), 2.86 (d, J=11.3 Hz, 1H), 2.58 (d, J=12.3 Hz, 1H), 1.87-2.11 (m, 2H), 1.50 (s, 9H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane
  3. additionadded
  4. concentrationAfter 1 h the mixture was concentrate
  5. customPurification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-9176d0351efd41c380436c9b69aa76fc
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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