Trifluoroacetic acid → HCID 73053232, compound

HRID 2275053Notes

Reaction equation

HRID 2275053 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([CH3:14])[N:10]([C:15]([C:17]2[CH:39]=[C:38]([O:40][CH3:41])[C:20]3[N:21]([CH3:37])[C:22]([C:24]4[N:32]([CH2:33][CH:34]5[CH2:36][CH2:35]5)[C:27]5=[N:28][CH:29]=[CH:30][CH:31]=[C:26]5[CH:25]=4)=[N:23][C:19]=3[CH:18]=2)=[O:16])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl.CO>[NH2:7][C@@H:8]1[CH2:9][N:10]([C:15]([C:17]2[CH:39]=[C:38]([O:40][CH3:41])[C:20]3[N:21]([CH3:37])[C:22]([C:24]4[N:32]([CH2:33][CH:34]5[CH2:36][CH2:35]5)[C:27]5=[N:28][CH:29]=[CH:30][CH:31]=[C:26]5[CH:25]=4)=[N:23][C:19]=3[CH:18]=2)=[O:16])[C@H:11]([CH3:14])[CH2:12][CH2:13]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118178631tert-Butyl((cis)-1-(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-6-methylpiperidin-3-yl)carbamate

Product 1

HCID 73053232HCID 73053232, compoundYield 90.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a flask containing tert-butyl((3S,6R)-1-(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-6-methylpiperidin-3-yl)carbamate (47 mg, 0.082 mmol) in dichloromethane (DCM) (1 mL) was added TFA (0.253 mL, 3.28 mmol) and the reaction was stirred for 2.5 h. The reaction mixture was concentrated in vacuo to afford a brown oil. This was dissolved in methanol and loaded onto an SCX cartridge (5 g). It was eluted with methanol (3 column volumes) and product eluted as free base with 2M ammonia in methanol. The filtrate from the ammonia fractions was concentrated in vacuo to yield a yellow oil—((2R,5S)-5-amino-2-methylpiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (35 mg, 0.074 mmol, 90% yield). The free base (35 mg) was dissolved in dichloromethane (DCM) (1 mL) in a vial and HCl (2M in Et2O) (0.037 mL, 0.074 mmol) was added. The resultant suspension was sonicated for 5 min and allowed to stand for 15 min.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto afford a brown oil
  3. washIt was eluted with methanol (3 column volumes) and product
  4. washeluted as free base with 2M ammonia in methanol
  5. concentrationThe filtrate from the ammonia fractions was concentrated in vacuo

Sources & evidence

ORD record
ord-3d8c146c7c284a91bd39dbf9975b1700
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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