Trifluoroacetic acid → (S)-4-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)but-3-ynyl 2-aminopropanoate

HRID 1984106Notes

Reaction equation

HRID 1984106 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([Cl:27])[C:5]2[C:10]([C:11]#[C:12][CH2:13][CH2:14][OH:15])=[CH:9][N:8]([CH2:16][C:17]3[C:22]([CH3:23])=[C:21]([O:24][CH3:25])[C:20]([CH3:26])=[CH:19][N:18]=3)[C:6]=2[N:7]=1.C([NH:35][C@H:36]([C:38](O)=[O:39])[CH3:37])(OC(C)(C)C)=O.CCN=C=NCCCN(C)C.C(O)(C(F)(F)F)=O>CN(C1C=CN=CC=1)C.CC(N(C)C)=O.C(Cl)Cl.O.CCOC(C)=O>[NH2:35][C@@H:36]([CH3:37])[C:38]([O:15][CH2:14][CH2:13][C:12]#[C:11][C:10]1[C:5]2[C:4]([Cl:27])=[N:3][C:2]([NH2:1])=[N:7][C:6]=2[N:8]([CH2:16][C:17]2[C:22]([CH3:23])=[C:21]([O:24][CH3:25])[C:20]([CH3:26])=[CH:19][N:18]=2)[CH:9]=1)=[O:39]

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 85082Tert-butoxycarbonylalanineHCID 119505104-[2-Amino-4-chloro-7-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-but-3-yn-1-ol

Product 1

HCID 57713853(S)-4-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)but-3-ynyl 2-aminopropanoate

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[2-Amino-4-chloro-7-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-but-3-yn-1-ol (see example 2) (51.7 mg), N-Boc alanine (53.3 mg), DMAP (33.7 mg), and EDCI (54.9 mg) in anhyrous DMA (4 mL) was stirred at rt overnight. Work-up (EtOAc; H2O) gave the crude Boc-protected intermediate. A solution of this intermediate (40 mg) in DCM (1.0 mL) was treated with TFA (0.2 mL) at rt for 5 min, and evaporated. The material was dissolved in MeOH (1 ml) and water (10 mL), and washed with Et2O (10 mL). The organic layer was discarded. The aqueous layer was brought to pH >7 with sat. aq. NaHCO3 and back-extracted with DCM. The title compound was isolates as a solid. HPLC Rt=4.37 min.

Workup

  1. customgave the crude Boc-
  2. customevaporated
  3. dissolutionThe material was dissolved in MeOH (1 ml)
  4. washwater (10 mL), and washed with Et2O (10 mL)
  5. extractionback-extracted with DCM

Sources & evidence

ORD record
ord-dba5b54c258c4d539f6dd8a9bb21b244
Source dataset
uspto-grants-2009_06
Patent number
US07544672B2

Reaction notes

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