Methyl chloroformate → HCID 86677806, compound

HRID 1499880Notes

Reaction equation

HRID 1499880 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[CH:21]=[C:20]([Cl:22])[C:17]([C:18]#[N:19])=[C:16]([CH:23]4[CH2:26][NH:25][CH2:24]4)[C:15]=3[O:27][CH3:28])[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12.C(N(CC)CC)C.Cl[C:37]([O:39][CH3:40])=[O:38]>ClCCl.CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:27][CH3:28])=[C:16]([CH:23]4[CH2:24][N:25]([C:37]([O:39][CH3:40])=[O:38])[CH2:26]4)[C:17]([C:18]#[N:19])=[C:20]([Cl:22])[CH:21]=3)[CH3:13])[N:9]=[C:10]([CH3:11])[C:3]=12

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 86677799HCID 86677799, compound2×

Product 1

HCID 86677806HCID 86677806, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-6-chloro-3-methoxybenzonitrile (chiral intermediate from Example 261) (20 mg, 0.05 mmol) in dichloromethane (1 mL) was treated with triethylamine (20 μL, 0.14 mmol) followed by methyl chloroformate (4.7 μL, 0.06 mmol) and stirred at room temperature for 1 h. The reaction mixture was diluted with methanol and purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (12 mg, 52%). The product was isolated as a single enantiomer. 1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.51 (s, 1H), 7.34 (br s, 2H), 6.25 (q, J=7.0 Hz, 1H), 4.53-4.38 (m, 1H), 4.36-4.17 (m, 4H), 3.71 (s, 3H), 3.55 (s, 3H), 2.55 (s, 3H), 1.73 (d, J=7.1 Hz, 3H). LCMS for C21H23ClN7O3 (M+H)+: m/z=456.2; Found: 456.1.

Workup

  1. custompurified by preparative LCMS (XBridge C18 column
  2. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-67a00131a80c42b0b47bf0ae0ecdacb6
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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