tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate → HCID 25254780, compound

HRID 1880897Notes

Reaction equation

HRID 1880897 reaction equation
[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=[N:49][C:44]2C=[CH:46][CH:47]=[N:48][C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N1CC[C@H](N)C1)(OC(C)(C)C)=O>>[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([NH:49][C@H:44]5[CH2:46][CH2:47][NH:48][CH2:43]5)=[O:29])=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 3

HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252536804-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

Product 1

HCID 25254780HCID 25254780, compound

Procedure

The title compound was synthesized from 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and (S)-1-N—Boc 3-amino pyrrolidine. The final compound was purified by reverse phase HPLC and basified to give the free base. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml). The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09-1.28 (m, 1 H) 1.30-1.47 (m, 2 H) 1.51-1.72 (m, 4 H) 1.73-1.88 (m, 4 H) 1.90-2.06 (m, 1 H) 2.64 (dd, J=11.24, 4.93 Hz, 1 H) 2.75 (ddd, J=10.67, 7.89, 6.44 Hz, 1 H) 2.82-3.03 (m, 2 H) 3.31 (s, 3 H) 3.94 (s, 3 H) 4.06 (t, J=13.52 Hz, 2 H) 4.23-4.37 (m, 1 H) 4.39-4.53 (m, 1 H) 7.44-7.50 (m, 1 H) 7.51 (d, J=1.52 Hz, 1 H) 7.90 (s, 1 H) 8.21 (s, 1 H) 8.23 (d, J=7.07 Hz, 1 H) 8.26 (d, J=8.34 Hz, 1 H). Melting point: 258-263° C. [M+H] calc'd for C26H33F2N7O3 530; found 530.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. customThe final compound was purified by reverse phase HPLC
  3. customto give the free base
  4. washFurther, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group
  5. customwas removed
  6. customThe final compound was purified by reverse phase HPLC
  7. customto give the free base

Sources & evidence

ORD record
ord-81f6b39103914e25b428f61cd57a1d39
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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